To determine risk factors for GBS colonisation in Gambian mothers and in their infants from birth to day 60–89 of age.Swabs and breastmilk from mothers/infant pairs were collected and cultured on selective agar. Negative samples were analysed for GBS DNA via real-time PCR. Positive isolates were serotyped using multiplex PCR and gel-agarose electrophoresis.Seven hundred and fifty women/infant pairs were recruited. 253 women (33.7%) were GBS-colonised at delivery. The predominant serotypes were: V (55%), II (16%), III (10%), Ia (8%) and Ib (8%). 186 infants were colonised (24.8%) at birth, 181 (24.1%) at 6 days and 96 at day 60–89 (14%). Infants born before 34 weeks of gestation and to women with rectovaginal and breastmilk colonisation at delivery had increased odds of GBS colonisation at birth. Season of birth was associated with increased odds of persistent infant GBS colonisation .GBS colonisation is common in Gambian women at delivery and in their infants to day 60−89 and is dominated by serotype V. In addition to maternal colonisation, breastmilk and season of birth are important risk factors for infant GBS colonisation. •Increased risk of infant GBS colonization is associated with maternal rectovaginal and breastmilk colonization.•GBS serotype V is a major colonizing serotype in the Gambia, thus this antigen should be included in candidate vaccines.•Midwife delivery, number of antenatal visits and season of birth are additional risk factors in low-income settings. Group B Streptococcus (GBS) is a leading cause of neonatal infection worldwide and transmission occurs mainly from mother to child during the peripartum period.The current leading candidate for maternal vaccination is a trivalent capsular polysaccharide protein conjugate vaccine containing ST Ia, Ib and III which is based on data on invasive disease serotypes in the USA, UKWe undertook a prospective longitudinal cohort study in two government health centres offering antenatal care to women in the Fajara area of costal Gambia, a low-income country with an annual birth rate of 43.1/1000 population, neonatal sepsis rate of 4.42/1000 live birthsThe eligibility criteria for maternal participation in the study included all pregnant women over the age of 18 years who had a negative HIV test and were deemed to be at low risk for pregnancy complications . Women were invited to deliver at the health centre and offered a confirmatory HIV test prior to enrolment. Women found to be HIV positive were referred for specialist ongoing care. Mothers were excluded if they were not planning to breastfeed or were unable to remain in the Fajara area for the first three months postpartum. Healthy infants over 32 weeks of gestation assessed using the Ballard score and weighing over 2.5 kg were included. Infants were excluded if they had obvious congenital abnormalities or required resuscitation at the time of delivery requiring transfer to a neonatal unit. Mother and infant pairs were recruited to the study between 1st January 2014 and 31st December 2014 if both mother and infant met the inclusion criteria. All eligible women and infants were recruited until the pre-defined sample size was reached. Participants were followed up daily at home until day 6 and then asked to return to clinic when the infant 60−89 days old for final follow up visit and vaccinations. If an infant died during the study a verbal autopsy was carried out to assess the potential cause of death.Field workers explained the purpose of the study to eligible participants in their local language  and each participant signed an informed consent form, or in case of illiteracy, thumb-printed and the consent form was signed by an impartial witness. The study was approved by the joint Gambian Government/Medical Research Council Research Ethics Committee, SCC 1350 V4.Rectovaginal swabs were taken from enrolled women presenting in labour to one of the health centres and cord blood was taken after delivery but prior to separation of the placenta. A screening questionnaire was completed after four hours postpartum and the infant checked for any abnormalities requiring medical intervention. The questions included ethnic origin, gravida, parity, maternal weight, blood pressure, haemoglobin concentration, use of medication/traditional medicines/antibiotics and vaccination in pregnancy, any illnesses in pregnancy, number of antenatal attendances, HIV status, education, diet, compound location and presence of cattle at the compound. Nasopharyngeal and rectal swabs were taken from all eligible infants at four hours after birth. Mothers were provided with soap and asked to wash their hands and wipe their breasts with alcohol wipes before hand expressing colostrum/milk within the first 12 h after birth, at day 6 and between days 60 and 89. Nasopharyngeal and rectal swabs were also taken from infants at day 6 of life and again at 60–89 days of life. Infants who were unwell before day 6 were assessed at home and referred for treatment as necessary. All sick infants had a blood culture taken on admission to hospital. At each visit a standardized questionnaire was completed in the local language documenting infant anthropometry, feeding, vaccinations, signs and symptoms of infant illnesses, use of antibiotic/traditional medicine and vital signs.Copan  and Dacron  swabs were collected in skim-milk tryptone glucose glycerol (STGG) transport medium, stored at 4 °C and transported to the Medical Research Council laboratories, The Gambia within 4 h of collection. On arrival the samples were vortexed briefly and immediately frozen at −70 °C until processing.All swab specimens were inoculated into Todd–Hewitt broth supplemented with colistin and nalidixic acid and were processed for isolation of GBS using standard laboratory procedures.The primary outcome was prevalence of ST-specific GBS colonisation in mothers and infants at birth, six days and between days 60–89 using microbiological culture and molecular techniques. Secondary outcomes were detection of GBS in breastmilk; infant acquisition and loss of GBS colonisation during the study follow up period and infant GBS disease (sample obtained from sterile site), as ascertained by positive microbiological culture and confirmatory PCR. Swabs were considered negative if no GBS was evident by culture and PCR and positive if GBS was found on culture and PCR. If swabs were negative on culture but positive on PCR, conventional PCR was performed to determine serotype. If the second PCR resulted in the identification of a GBS serotype the samples were deemed positive. If no serotype was identified or the DNA did not amplify, samples were deemed negative.Calculated on the basis of the previously observed 24% colonisation rate,Statistical analyses were completed using STATA version 12  and GraphPad Prism version 6.0 . Descriptive statistics included the prevalence of colonisation at individual time points expressed as a proportion of the total number of participants. Odds ratios and 95% confidence intervals (CI) were calculated to determine risk of maternal and infant colonisation at birth in a single variable analysis. Adjusted odds ratios were then calculated using any variables from the single variable analysis with a p-value <0.2 using a backwards-stepwise procedure.Analyses of the changes in infant colonisation over time were undertaken using longitudinal logistical regression. Adjusted odds ratios were then calculated using any variables from the single variable analysis with a p-value <0.2 using a backwards-stepwise procedure. New acquisition of GBS was defined as detection of a new serotype by culture or PCR that was not previously present. Clearance of colonisation was defined as a negative GBS culture or PCR for a specific serotype following a positive sample at the previous visit for the same ST. The log-rank test was used to examine differences in duration of colonisation between serotypes. Using an expected vertical transmission rate of 50%The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data and the corresponding author had final responsibility for the decision to submit for publication.Between 15th January 2014 and 31st January 2015 we recruited a total of 750 mothers and their infants to the study. All mothers met the inclusion criteria except one, who was admitted to hospital on day three post-partum severely unwell and subsequently tested positive for HIV1, despite a negative test at 20 weeks of gestation. She and her infant were referred for further management and samples excluded from further analysis. Of the remaining eligible women and infants, 722 completed the day 6 visit  and 684 completed 60–89 days follow up . The main reasons for not completing follow up were: 31 women moved out of area, 20 women whose partners were not in agreement with continued study participation, one maternal HIV, nine infant deaths, five declined for other reasons. Participant flow diagram and demographic characteristics of mother–infant pairs are outlined in Over the course of the study, 77 women received antimicrobials during pregnancy: 34 for urinary tract infection; 10 for pneumonia; 14 for vaginal discharge; 9 for malaria and 10 for non-malarial fever. Of these, 73 women received amoxicillin (median time prior to delivery 42 days [IQR 18–63 days]); 16 received antimalarial therapy (median 38 [31–41]) and three received erythromycin. In the three months of follow up, 51 infants required antibiotic therapy: 34 received ampicillin and gentamicin for presumed neonatal sepsis (median 18 days old [IQR 4–34]); 10 received amoxicillin or cloxacillin for skin infections (20 days [10–58]); 7 received other antibiotics (18 days [11–23]). Antibiotic therapy was included in adjusted analyses and had no impact on colonisation of mother or infant at any time point.The overall prevalence of recto-vaginal GBS colonisation at delivery was 33.7% (253 women). In single variable analysis maternal weight >50 kg, maternal haemoglobin <10 g/dL, more than one previous stillbirth, more than one antenatal clinic visit, midwife delivery, giving birth during the dry hot or wet seasons, birth weight over 3 kg and gestation under 34 weeks were associated with increased risk of GBS colonisation . In adjuThere were 253 colonised mothers and 186 colonised infants at birth, of whom 146 were born to colonised women (57.7%). Compared to mother/infant pairs who were not colonised at birth, mother/infant pairs were more likely to both be colonised if mother's weight was below 50 kg, infant was born at less than 37 weeks of gestation, born during the dry hot or wet seasons, mothers with more than one previous stillbirth, mothers attending antenatal clinic more than once, infants delivered by midwives, infants born with a birth weight below 3.3 kg or receiving breastmilk colonised with GBS .In adjusted analysis, compared to mother/infant pairs who were not colonised at birth, mother/infant pairs were more likely to both be colonised if birth occurred in the dry hot or wet seasons, mothers with one or more previous stillbirths or spontaneous abortions, infants born before 34 weeks of gestation. Compared to mother/infant pairs where neither was colonised, mother/infant pairs where the mother was colonised but not the infant were more likely if the mother had more than one previous stillbirth, or if the mother gave birth during the wet season. Infant colonisation in the absence of maternal colonisation (n = 40) was associated with gestation before 34 weeks .Most notably, compared to mother/infant pairs at birth where neither were colonised, infants born to mothers who had GBS cultured in their breastmilk were more likely to be colonised with GBS .Infants born to colonised mothers had an increased risk of colonisation at birth and day 6–9 if born during the dry hot season or if born before 34 weeks of gestation. For all variables the risk of colonisation decreased over time .Infants born to non-colonised mothers had an increased risk of being GBS colonised on day 6–9 and at day 60–89 if born during the wet season. At birth infants were more likely to be colonised if breastmilk was colonised and they remained more likely to be colonised at both 6–9 days and day 60–89.2 = 24.4, p < 0.001) compared to mothers colonised with other serotypes. The predominant maternal rectovaginal colonising serotype was ST V in 54.9% of colonised mothers. Mothers' breastmilk was more likely to be colonised with ST V (p < 0.001) at all time points than any other serotype. Infants were more likely to be colonised with ST V at birth (p = 0.004), day 6–9 (p = 0.004) and day 60–89 (p = 0.009) than any other serotypes. At birth, infants were more likely to be colonised with ST III and V if their mothers were colonised with ST III and V  presented with signs of infection (68 per 1000 live births): 18 with signs of pneumonia, 22 with signs of other febrile illness, ten with skin infections and one with signs of meningitis. One child presenting on day 6 of life with irritability and poor feeding, had a positive CSF culture for GBS and was treated for 21 days with ampicillin and gentamicin (invasive GBS disease incidence: 1.3 per 1000 live births). This infant was born to a mother who had ST V cultured from both rectovaginal swab and breastmilk at birth and day 6 of life and the infant swab was also positive at birth and day 6 for ST V. The CSF sample was not typed due to laboratory constraints.Nine infants died during the study period. Based on verbal autopsy, six deaths were due to pneumonia (median age at death 7 days [IQR 2–35]); three due to sepsis (median age 6 days [1–48]). Blood cultures were negative in all cases. One infant was born to a colonised mother and was also colonised with GBS at the time of birth but was not colonised on day 6. This infant died of presumed sepsis on day 48 of life. No other infants who died or their mothers were colonised with GBS at time of birth or day 6 of life. All infants died prior to the final follow-up appointment. It is therefore, not possible to determine whether any of these deaths were due to GBS disease.In this first colonisation study of Gambian mothers and their infants for 25 years and the first longitudinal study undertaken in this population, we demonstrate high prevalence of GBS colonisation in mothers at birth and in their infants up to 90 days of life. In addition, we demonstrate that infants were more likely to be colonised if GBS was isolated from their mother's breastmilk. The overall prevalence of maternal GBS in our population is higher than in the original study by Suara et al. (1992) (Suara 22% colonised (95% CI 15.04–28.96) vs. present study 33.7% colonised (29.63–36.37); p = 0.007).Our finding that mothers with more than one stillbirth demonstrated an increased odds of having a colonised infant are in concordance with Monari et al., who identified stillbirth as a risk factor for invasive EOGBS disease.The prevalence of infant colonisation in our study is similar to previous studies in EuropeSeveral case reports suggest that isolation of GBS in breastmilk is implicated in late onset GBS disease.It is interesting to note that risk factors for maternal colonisation include midwife delivery and increasing number of antenatal visits. This phenomenon has not been previously noted in resource-poor settings where hygienic birth practices may be compromised. GBS has been implicated in nosocomial outbreaks in several hospitals globally,A large proportion of women were colonised with ST V, similar to the previous smaller study by Suara et al., which identified 32 colonised pregnant women of whom 12 (30%) were colonised with ST V.Our study has several limitations. First, our results are limited by the sensitivity of detection of GBS on selective media, estimated at 85%GBS capsular polysaccharide-protein conjugate vaccines are being developed, making the findings of our study important to ensure that appropriate serotypes are included in candidates that would be relevant to all African populations. Information about GBS colonisation and factors affecting acquisition and duration of colonisation will be helpful in considering strategies for reducing the burden of infant GBS disease worldwide.KLD conceived the original idea, designed and performed the laboratory and data analysis and drafted the manuscript. SJ and SD performed and interpreted the laboratory analysis and contributed to the manuscript preparation. AG, PH and BK developed the original research idea and contributed to the manuscript preparation. FW advised on the statistical analysis and commented on drafts of the manuscript.Wellcome Trust Clinical Research Fellowship to KLD (WT104482MA) and the Thrasher Research Fund (BK: 12250). BK is also supported by grants from the UK MRC  and the UK Medical Research Council (MRC) and the Department for International Development (DFID) under the MRC/DFID Concordat arrangement.This work was supported by a KLD, SJ, SD, AG declare no conflict of interests. PTH is an advisor to Novartis and Pfizer regarding GBS vaccines. BK is an advisor for Pfizer regarding GBS vaccines.


To assess whether the parents of babies born preterm  are at excess risk of psychological distress (PD) at 9 months postpartum, and to explore the influence of the degree of prematurity.Data were drawn from the UK Millennium Cohort Study, a nationally representative prospective cohort of babies born in 2000–2002. 12 100 families with complete data available for both parents at recruitment (9 months postpartum) are included.Mothers report of gestational age at birth (in weeks) was grouped into: very PT (<32 weeks), moderately PT (32–33 weeks), late PT (34–36 weeks), early term (37–38 weeks), full-term (39–41 weeks), post-term (42 weeks). PD was assessed using a modified Rutter Malaise Inventory, a validated instrument that has been used in both men and women to assess levels of anxiety and distress.Overall, 7% of families reported a PT birth; 12.1% of mothers and 8.9% of fathers showed signs of PD at 9 months postpartum. The mothers of very PT infants had an increased risk of PD, compared with the mothers of full-term babies ). Mothers of moderate or late PT babies had no apparent increased risk of PD. However, mothers of early term babies also showed a small excess risk of PD (adjusted OR 1.16 (0.99 to 1.36)). Unadjusted analysis suggested a doubling in the risk of PD in fathers of very and moderately PT babies, compared with fathers of full-term babies, which remains statistically significant after adjustment in the moderately PT group (adjusted OR1.98 (1.20 to 3.29)).The parents of very PT children are at an increased risk of PD at 9 months postpartum, and mothers of children born at early term also see an elevated risk compared with mothers of full-term babies. This is a nationally representative sample of over 12 000 families, with data on both the mother and father and gestational age. Gestational age was used in the analysis, rather than preterm birth, to examine whether degree of prematurity was important.A validated measure of psychological distress was used as the outcome, and a wide range of important confounders were considered in the analysis.The sample was restricted to families with both parents resident in the home at 9 months. No data were available on timing of past depressive episodes in either parent or on antenatal depressive symptoms in mothers.Becoming new parents, or having another baby, while marked by excitement, is often also marked by disturbance in mood. Most commonly depressive symptoms have been measured with screening indicating that an estimated 10–18% of new mothers, depending on time of assessment, experience such symptoms.It is recognised that stressful life events can trigger PD,15In both mothers and fathers, the literature provides conflicting evidence with some reporting a negative effect of PTB on mental health,PD, and in particular depression, is known to have a negative impact on the individual, their relationships and family life,For these reasons, it is necessary to examine whether the mothers and fathers of preterm children are at greater risk of PD beyond the neonatal period, and whether the effect differs by degree of prematurity. This study explores how the extent of prematurity impacts on subsequent PD in both mothers and fathers in the first year, through secondary analysis of existing data from the UK Millennium Cohort Study (MCS).The Millennium Cohort Study is a nationally representative prospective cohort study of 18 552 families across the UK. A random two-stage sample of all infants born in 2000–2002 and resident in the UK at 9 months was drawn from Department of Social Security (DSS) Child Benefit Registers. Ethnically diverse and disadvantaged areas were oversampled to ensure adequate representation. Children were identified by the DSS responsible for administering the benefit, who then sent a letter and information leaflet to the selected families giving them an opportunity to opt-out of the survey. Ethical approval for the survey, including the use of opt-out procedures for consent, was granted by the South West Medical Research Ethics Committee (MREC/01/6/19). Interviews with both parents were conducted when the cohort children were 9 months old, on average, and captured sociodemographic and health information, including details of depression and current mood. The cohort study does not cover births where the infant died within the first 9–10 months after birth, but these constituted less than 1% of all births. In total, 18 495 (99.6%) biological mothers and 13 167 (71%) of partners provided details about their children and about themselves, through computer-assisted questionnaires and interviews.The main outcome of interest is symptoms of PD. This analysis includes those families where both parents completed the modified Rutter Malaise Inventory (RMI) as part of the self-administered questionnaire 9 months after the birth of their baby, and who have complete data for covariates . The RMI was developed as a self-completion scale in simple language to cover one underlying latent construct of ‘emotional disturbance’,This modified RMI scale includes yes/no questions about nine affective and physical symptoms of depression and anxiety. An overall score was calculated, and a dichotomous outcome was derived, where modified RMI score >4 indicates signs of depression or PD , educational attainment ), highest socioeconomic class of the partnership, currently employed, ethnicity;Pregnancy and perinatal variables: unplanned pregnancy , mode of delivery , parity (first birth or not), singleton or multiple pregnancy, any breast feeding for 4 months or longer (reflecting the recommendation at the time of survey). Birth weight was not included, as it is highly correlated with the main outcome, prematurity.Items were considered as potential confounding factors if they were independently associated with the outcome, and remained statistically significant at the 5% level when added to the multivariable logistic regression model.All analyses were conducted in Stata V.13,In total, 12 100 families are included in the analysis, of whom: 1% of babies were very preterm , 1% were moderately preterm , 5% late preterm , 20% early term  and 69% were full-term . Three per cent of babies were reported as delivered post-term . The characteristics of the study population are described in The average age of parents was 29.7 years for mothers and 32.3 years for fathers, and there was little variation over the gestational age groups. About half of all families (51.5%) were in the highest socioeconomic group which is higher than for the MCS overall as our study population was restricted to families in which both parents lived together and responded to the modified Rutter questionnaire. However, within our study population, a greater proportion of the families of very preterm babies was of lower socioeconomic status and had parents without educational qualifications. Overall, 8.5% of fathers and 8% of mothers described themselves as Black and Minority Ethnic group (BME), but the proportions were higher in the very and moderately preterm groups . The prevalence of unplanned pregnancies rises with increasing prematurity. Emergency caesarean section was reported in 12.9% of births, but this was markedly different across the groups, with 56.0% of the very preterm being delivered in this manner, compared with 11.2% in the full-term. Elective caesarean section was seen in 10.1% of all births, but was significantly more common in the early term group, where 26.4% of mothers reported an elective section delivery.In total, 12.1% of mothers showed signs of PD at 9 months postpartum; the prevalence of PD was highest in the very preterm group, but dropped in the moderately preterm group and remained lower over the rest of the spectrum, as shown in The unadjusted analysis suggests that the mothers of infants born at less than 32 weeks (very preterm) were more than twice as likely to be showing signs of PD at 9 months, compared with the mothers of the babies born at term (OR 2.10 (1.30 to 3.39), p<0.05). This statistically significant effect persisted after adjustment for confounding, although it was reduced (OR 1.66 (1.02 to 2.69), p<0.05). However, there was no evidence that the mothers of moderate or late preterm babies had an increased risk of PD. In unadjusted analysis, the mothers of the early term babies were also at a small increased risk of PD (OR 1.19 (1.02 to 1.40), p<0.05), and the effect remained similar after adjusting for confounding (fully adjusted OR 1.16 (0.99 to 1.36), p=0.06), as shown in Fewer fathers than mothers showed signs of PD, just 8.9% overall. Prevalence was highest in the very preterm (16.1%) and moderately preterm (16.8%) groups see . In the PD is highly associated in mothers and fathers in this cohort, so that in families where mothers are showing signs of PD, fathers are more than twice as likely to also be in the PD category (OR 2.22 (1.87 to 2.66), p<0.05). However, in absolute terms, the overlap is small—in 80.9% of families neither parent showed PD, in 10.2% only the mother and in 7.0% only the father was in the PD category, and only 1.9% of families (n=277) had both parents in the PD category.While 30.5% of all mothers reported feeling low or sad for 2 weeks or more since the birth, this figure was 65.1% in the very preterm and 48.3% in the moderately preterm. The mothers of the very preterm group were also more likely to be receiving current treatment for depression, although numbers are relatively small, hence this outcome is not further explored. Only 2.3% of fathers reported that they were currently receiving treatment for depression, but again the prevalence was higher in the most preterm group . This increase in risk in the very preterm group is consistent with the sparse literature describing the association between gestational age and parent's mental health, where others have also suggested that degree of prematurity is an important factor for maternal depressive symptoms.The adverse effect of having a very preterm baby is likely to act through a number of mechanisms, so that it is partly the shock of having a very early delivery and partly the longer term stress of having a preterm infant who is more likely to be in poor health in their first year. Studies of parents of PTB have identified high rates of post-traumatic stress disorder, resulting from the unexpectedly early transition to parenthood before parents had adequate time to prepare either mentally or practically. Very preterm babies are also likely to need complex interventions including ventilation and incubation, to spend more time in neonatal care, and to have early feeding difficulties, all of which are very stressful for parents.Our results show that mothers who delivered their babies in the early term group are also at a slight increased risk of PD, compared with those in the term group. However, here it seems less plausible that it is as a result of the stress of dealing with a very ill baby, as in general children born at this gestational age are healthy. The mechanism may instead act through the mother's own health or later pregnancy complications.The fact that no effect was observed in the late preterm  may be partly explained by the step change in infant health that occurs at about 32 weeks’ gestation. Prior to this, the increase in the risk of severe morbidity (such as retinopathy of prematurityThis study of over 12 000 families draws on a nationally representative cohort study with a good response rate, and employed weights to account for non-response and design effects due to stratified sampling. The effects of new fatherhood are often overlooked but we analysed data on both mothers and fathers in cohabiting relationships, so that the effects on both parents could be assessed. However, as the MCS did not collect data on non-resident fathers, our study does not include lone parents for whom the impact of a PTB or sick infant may be even more detrimental due to a lack of support from a partner.Detailed maternal report on delivery allowed us to look at the effects across the continuum of gestational age. Gestational age and birth weight were validated against hospital records, and implausible values were removed, so that we are confident in the gestational age groups reported here. Relatively small numbers of cases in the moderately and very preterm groups does mean that the effects seen here should be treated with caution, although the results are consistent with the findings of other studies.16–18The MCS used the modified RMI in the survey at 9 months, which is a validated measure of PD; the instrument has been used in a number of cohort studies.In women, antenatal depression is associated with PTB,both parents of very preterm babies are at risk of PD. Further research on the impact of PTB of the mental health of parents is needed, so that there can be increased vigilance for symptoms of PD in this group. Where symptoms are identified early and support can be given, the negative impacts of PD on the individual and their family could be reduced.This study suggests that both mothers and fathers of very preterm babies are approximately twice as likely to experience symptoms of PD at 9 months postpartum, and though this effect is reduced after adjusting for confounding factors, it does not disappear. Fathers in the moderately preterm group also show an increased risk of PD, but this is not mirrored by the mother's risk. A novel finding is that mothers in the early term group are also at a small increased risk of PD: this should be a focus for future work as the early term group represents a large proportion of all births, and so the impact of this small increase in risk on maternal well-being at the population level will be greater. Small numbers in the most preterm groups, and a lack of data on antenatal depression, mean that the estimates should be treated with caution but, in general, the results for the preterm groups are in line with the existing, sparse literature. Significantly, the findings suggest that


Juvenile systemic lupus erythematosus (JSLE) is a chronic, autoimmune and multisystem disease. Adult patients with SLE have an elevated risk of premature atherosclerosis and myocardial infarction. Dyslipidemia is a risk factor for the development of future chronic diseases and is associated with disease activity, corticosteroids use (CTC), renal impairment, among other factors.Other biochemical markers have been proposed for identification of cardiovascular risk, among them the protein components of lipoproteins (apolipoproteins - Apo) and enzyme related to cardiovascular risk (paraoxonase - PON).To evaluate the biochemical markers related to cardiovascular risk in adolescents with JSLE.Cross-sectional and controlled study including 33 female adolescents with JSLE and 33 healthy controls. We evaluated: lipid profile, Apo A1, Apo B, PON activity and body mass index (BMI). For classification of lipid profile we considered cutoff points proposed by the American Academy of Pediatrics. Statistical analysis: Mann-Whitney test.The median age and SLEDAI of the patients were 16 years and 2 , respectively. We observed SLEDAI > 4 in 33 %, nephrotic syndrome in 12%, CTC use in 75.8% [median dose 0.18  mg/kg/day] and hydroxychloroquine use in 93.9% of the patients. Overweight/obesity was observed in 36.4 %; dyslipidemia in 39.4 and 21.2 % of patients and controls, respectively. Hypertriglyceridemia and low HDL -C were the most frequent alterations. Apo A1 concentrations were significantly higher in controls (p = 0.01). There was no statistical difference in the lipid profile, in the concentrations of Apo B (p = 0.85) and in PON activity (p = 0.062). There were statistical differences in the relations Apo B/Apo A (p = 0.000) and LDL/Apo B (p = 0.000).Low concentrations of Apo A1 in patients suggest a dysfunctional HDL cholesterol, possibly due to inflammation. The results indicate increased cardiovascular risk in adolescents with JSLE compared with healthy controls.None declared


Using a dataset of ∼450,000 participants from the UK Biobank study, we aimed to assess the impact of this seasonality on birth weight, age at menarche, adult height and body mass index (BMI). Birth weight, age at menarche and height, but not BMI, were highly significantly associated with season of birth. Individuals born in summer (June–July–August) had higher mean birth weight (P = 8 × 10−10), later pubertal development (P = 1.1 × 10−45) and taller adult height (P = 6.5 × 10−9) compared to those born in all other seasons. Concordantly, those born in winter (December–January–February) showed directionally opposite differences in these outcomes. A secondary comparison of the extreme differences between months revealed higher odds ratios [95% confidence intervals (CI)] for low birth weight in February vs. September , for early puberty in September vs. July  and for short stature in December vs. June . The above associations were also seen with total hours of sunshine during the second trimester, but not during the first three months after birth. Additional associations were observed with educational attainment; individuals born in autumn vs. summer were more likely to continue in education post age 16 years (P = 1.1 × 10−91) or attain a degree-level qualification (P = 4 × 10−7). However, unlike other outcomes, an abrupt difference was seen between those born in August vs. September, which flank the start of the school year. Our findings provide support for the ‘fetal programming’ hypothesis, refining and extending the impact that season of birth has on childhood growth and development. Whilst other mechanisms may contribute to these associations, these findings are consistent with a possible role of in utero vitamin D exposure.Season of birth, a marker of  The most compelling associations to date appear to be those with immune-related disease (ID) 3 levels also vary markedly by season of birth, with almost two-fold higher levels in summer compared to winter births reported in a Danish population study Various mechanisms have been suggested to underlie month of birth associations, including seasonal differences in maternal exposure to meteorological factors (such as sunshine), air pollution, food supply, diet and physical activity Under the hypothesis that season of birth associations are primarily driven by changes to circulating 25(OH)D, we prioritised a previously untested trait for month of birth effects – puberty timing. Age at menarche is a well-recalled measure of pubertal timing in girls and has been linked to vitamin D status in prospective In up to 452,399 white UK Biobank participants born in the UK and Ireland, we identify robust associations between season of birth and early life growth and development.22.1The UK Biobank study design has been previously reported 2.22) and height in centimetres were measured at the assessment centre and treated as continuous outcomes, excluding individuals >4 SDs from the mean. A short stature case-control variable was additionally defined as the bottom 5% of individuals (within sex) vs all others.Our primary exposure of interest was season of birth, which was based on month of birth recorded in all study participants by questionnaire. We categorised the month of birth into seasons, defined as Spring (March–April–May), Summer (June–July–August), Autumn (September–October–November) and Winter (December–January–February). The primary outcomes of interest were the participants' birth weight, their height/BMI at recruitment, and among women, their age at menarche. Birth weight was recalled by questionnaire and reported in kilograms. Birth weight was treated both as a continuous quantitative trait and a case-control outcome, with weights below 1 Kg and above 6 Kg (approximating 4 standard deviations from the mean) excluded from analysis. Low birth weight cases were defined as < 2.5 Kg, controls were all birth weights >= 2.5 Kg. Age at menarche in women was self-reported in whole years, and women with a reported age < 8 or > 19 were excluded as outliers. Early menarche was defined as 8–11 years inclusive. Body mass index (Kg/mhttp://www.metoffice.gov.uk/pub/data/weather/uk/climate/datasets/Sunshine/date/UK.txt). For each individual, we calculated the cumulative hours of sunshine recorded for each month averaged across the UK in the 9 months preceding their birth month and the 3 months after. These were then grouped into four groups – three trimesters (including the month of birth) and the first 3 months after their birth month.We estimated maternal sunshine exposure using recorded data from the Met Office (−5 (0.05 / 185 traits × 4 seasons) for this untargeted analysis.Secondary analyses were performed across past or current diseases self-reported in response to the question “Has a doctor ever told you that you have had any of the following conditions? (You can select more than one answer)”. To ensure good discrimination between medical conditions, the data were collected using a computer-assisted personal interview (CAPI), administered by trained interviewers. To provide sufficient statistical power we considered only those diseases/outcomes with least 500 cases in either sex . In total, we considered 185 diseases or health outcomes which we previously defined and tested Three educational attainment variables were created in response to the touch-screen questionnaire completed by participants. Individuals who responded “prefer not to answer” were set to missing. Individuals who held a college or university degree , the age at completion of full-time education , and thirdly individuals reporting no listed qualifications .2.3Birth month and birth season variables were coded ‘1′ for the month/season of interest and ‘0′ for all others. Linear regression models were performed to test the association between birth season and each of our four primary outcomes . Prior to analysis, birth weight and estimated sunshine exposure were inverse-normally transformed to have a mean = 0 and SD = 1. Our significance threshold was set at P-value (0.05 / (4 traits × 4 seasons)) = 0.003 to declare a birth season effect. To ascertain the shape of any resulting associations, we additionally repeated the analyses using individual birth months as the exposure . All models were adjusted for age, sex (where appropriate) and socio economic position (SEP) defined by 11 principal components (PC) explaining > 99% of the trait variance 3255,769 individuals  had a self-reported birth weight > 1 kg, 9.8%  of whom reported low birth weight (< 2.5 Kg). Age at menarche between the ages of 8 and 19 years inclusive was self-reported in 238,014 women. Height and BMI measurements were available in 451,435 and 452,399 individuals, respectively after exclusions and covariate adjustments.3.1−25, N = 255,769) to −0.05 SDs for winter births (P = 3.8 × 10−29), with significant heterogeneity between sexes (summer and winter Phet < 0.05). Associations with month of birth varied continuously throughout the year (−15) and a trough in February . Associations with the dichotomised trait, low birth weight , showed similar patterns (−10), an effect which was significantly different between sexes (PHet = 0.02).Season of birth was associated with birth weight (as a continuous trait); each of the four seasons showed significant differences to the other 3 seasons . Effect the year , with a patterns . Individ3.2−45, N = 238,014) to −0.09 years for autumn births (P = 2.5 × 10−34). Associations with month of birth varied continuously throughout the year (−21) and trough in September . At the monthly extremes, individuals born in September were ∼20% more likely to enter puberty early  than those born in July (OR 1.22 (1.16–1.28), P = 7.3 × 10−15). These associations appeared independent of birth weight  to −0.13 cm for winter births (P = 1.2 × 10−9). Peak month of birth differences were seen between June vs. December: +0.31 cm taller height (P = 2.0 × 10−11) and lower risk of short stature . Among women, adjustment for age at menarche and birth weight attenuated the association between winter births and shorter adult height, but did not attenuate the association between summer births and taller adult height, and augmented the association between autumn births and shorter adult height . As expected, estimated sunshine exposure during the first trimester was strongly correlated with summer (r = −0.73) and winter births (r = 0.68), second trimester with spring (r = −0.74) and autumn (r = 0.67) births and third trimester with summer (r = 0.68) and winter (r = −0.72) births. Assessment of the three traits with significant seasonal effects demonstrated estimated sunshine exposure associations concordant with the observed season of birth associations . For eac3.5−5), no disease association was seen with any season of birth. We next assessed whether any of the covariates included in these models  was associated with season of birth. As expected, age and sex were not associated with season of birth , however several principal components of socio-economic position were (Pmin = 4 × 10−34). These associations were driven by a primary effect of season of birth on educational attainment (−79). The pattern of association between month of birth and educational attainment differed strikingly to those with birth weight, age at menarche and adult height, with an abrupt contrast between individuals born in September vs. August (education post-16: OR 1.43 [1.38–1.48]) (Het = 0.003).To assess the potential impacts of the season of birth associations on later health and other outcomes, we systematically tested associations between season of birth and a broad range of 185 disease outcomes. After correction for multiple testing  . Further4In this large study of ∼500,000 UK individuals, we describe the most comprehensive assessment to date of the impact of birth season on childhood growth and physical development. In support of several other studies Seasonality in childhood growth has long been described. Humans, and also animals, show fastest growth in spring and summer and slowest growth in autumn and winter 3 levels were reportedly associated with higher risk of adult overweight The lack season of birth associations observed here for adult BMI appear discordant to those recently reported by the Kadoorie Biobank study in utero. It remains unclear how these effects are programmed and what physiological mechanisms make them act years after the exposure. Through systematic assessment of almost 200 health/disease traits, we were able to eliminate any large effects of birth seasonality on many common diseases in the UK population. Due to the conservative multiple-test correction thresholds, it still remains possible however that season of birth may have modest effects on other previously unsuspected health outcomes, as seen in other populations Collectively our findings support the existing season of birth literature, refining and extending the impact this has on childhood growth and development. This provides direct support for the ‘fetal origins of adult disease hypothesis' that intra-uterine exposures impact health outcomes many years later Month of birth is highly likely to be randomised to confounding factors, and resulting associations are not subject to reverse causality. These associations therefore represent causal, rather than correlative, relationships with effect sizes similar to genetic determinants identified for these traits in utero vitamin D exposure on fetal growth, differing patterns of seasonality and independent associations suggest that other mechanisms may link season of birth to adult height and also puberty timing in women. Future work should aim to better understand the mechanisms linking in utero exposures to outcomes years later in life.In summary, we provide robust evidence linking season of birth to childhood growth and development, in addition to confirming the known associations of timing of birth and educational attainment. While the associations between season of birth, or estimated antenatal sunshine exposure, with birth weight are consistent with experimental effects of Felix Day, John Perry: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Wrote the paper.Ken Ong: Conceived and designed the experiments; Analyzed and interpreted the data; Wrote the paper.Nita Forouhi: Conceived and designed the experiments; Analyzed and interpreted the data.This work was supported by the Medical Research Council (Unit Programme number MC_UU_12015/2).The authors declare no conflict of interest.No additional information is available for this paper.http://www.ukbiobank.ac.uk.This research has been conducted using the UK Biobank Resource. Data associated with this study is available via application to UK biobank at


To explore the experiences of women from three population groups of immediate skin-to-skin contact (SSC) with their newborn babies.A mixed methods approach was adopted in a phenomenological study to elicit the experiences of English, Pakistani and Bangladeshi women. Audiotaped diaries, semi-structured interviews, photographs and video recordings were employed. Concept mapping was central to data analysis.This paper reports novel findings that women contextualized and accepted secretions and bodily fluids from birth. This contradicts the beliefs of midwives that Asian women find bodily secretions abhorrent and culturally unacceptable. All participants reported positive experiences of SSC despite varying degrees of soiling from birth fluids.The study was conducted in a single setting, and participants may not have been representative of others in their cultural groups. Third-party translation may have added an unsought layer of interpretation. The imposition of cultural expectations by peers in the recruitment process excluded some potential participants.Stereotypical assumptions about cultural background often characterize professional responses. When this stereotyping was put aside, women of all three cultures, whether breastfeeding or bottle-feeding, were able to enjoy SSC with their babies.The findings suggest that changes will be needed in professional practice to be more open to women's expressed preferences, in local policy to ensure that choices are made clear and are available, and in national strategic direction to ensure widespread adoption of positive practices for opportunities to increase breastfeeding, promote parent–child bonding and support patient choice to be realized. In the UK, policies have been introduced to reform maternity services, aiming to plan and deliver care that is more responsive to the needs of individual women and their families . The intChanging embedded beliefs and ritualized care is challenging and even more difficult to address when evidence to support the change is limited. This study was driven by a desire to fill a gap in knowledge about women's experience of SSC from diverse population groups. Ultimately, the goal was to answer a practical problem and to justify a change in midwifery practice. The women's own voices recounting their experiences were used to shape midwifery care. The intention was to provide evidence on whether or not immediate and prolonged SSC between all mothers and babies at the time of birth was acceptable.SSC is the placing of the newborn baby directly on its mother's skin immediately following birth. The baby is briskly dried and at once placed naked on its mother's skin, and then both the mother and the baby are wrapped in warm blankets. Strong evidence suggests that this simple, cost-free practice increases early feeding , particuYet there is evidence that some midwives are concerned about the contaminating secretions of birth: blood, amniotic fluid and mucus . They feTraditionally, particularly across cultural groups organized around religion, blood associated with menstruation and birth is noted to be polluting, contaminating and unclean. This is the case for Islamic families, orthodox Jewish communities, Sikhs and Hindus . HoweverCultural stereotyping remains widespread. The impact of separating a mother and infant is significantly demonstrated in the literature: inability to attune to the baby and to show love and affection ; reducedThe need to promote SSC for all babies is vitally important, then, regardless of feeding mode and cultural background. Moreover, it is important for health professionals to lay aside assumptions of cultural belief and expected response to birth fluids in order to allow an informed free choice for mothers of all cultures.An interpretive, Heideggerian, phenomenological approach was adopted, guided specifically by the work of Approval for the study was secured from an NHS research ethics committee and from the University of Salford research ethics committee. Care was taken in composing information sheets in formats that could be understood by women from the three groups under study and in a way that would not cause offence or distress.Twenty women who participated in the study had experienced 1 h or longer of uninterrupted SSC immediately following birth. They were recruited during the last 3 months of their pregnancy from a hospital maternity unit in England and were drawn from three cultural groups: Bangladeshi, English and Pakistani.Data collection by a variety of methods was completed in 2010. Digital recorders enabled participants to record a diary, video recordings shared visual data, and one participant used photography to capture and illustrate her experience. A great depth of understanding of phenomena can be gained using these methods. These activities empowered the women to reflect back to the time and situation and to record the associated memories, smells, sounds and feelings. Through this, they provided a rich perspective of that particular point in time. Video recorders were used by the partner or fixed on tripod stands to record the period of immediate SSC of four participants. This generated a large amount of visual data.Interviews were conducted with the participants using the recorded data as a focus and prompt for discussion. Each interview lasted between 1 and 2 h and the whole of the data collection took 2 years to complete. Interviews were conducted at home or in the hospital, the organization's ethnic health team providing synchronous translation when required. The process of interviewing was iterative rather than linear so that learning from one encounter was carried into the next. The women spoke freely and passionately about their experiences. Observational data during review of the video footage and interviews were included in contextual field notes.Analysis was cyclical, reflective and, at times, a messy process. When contextualized features of a lived experience are generated from a blend of meanings and understandings articulated by the researcher and participants, such as in this study, interpretive (Heideggerian) phenomenology provides the right framework . AnalysiThe behavioural units in the video recordings included gaze, head turns, speed of approach to the breast, facial expressions, small shifts in arousal and mother–infant vocalization. Concept maps  enabled In this study, mothers and babies clearly interacted with each other; the baby elicited responses from the mother, and the mother explored, touched, smelled and nurtured her infant intuitively. Yet, babies are not mere passive actors either. They are active communicators (as demonstrated in the video footage). They use systems of eye contact, cries and facial gestures to direct responses from their caretakers. This relationship, which develops during pregnancy and extends after birth, shapes and changes the brains of mother and infant.For some Asian women in the study, blood, mucus and amniotic fluid were found acceptable in the context of birth; yet, the same secretions were seen to be dirty, polluting and contaminating outside of this context. Aisha showed no revulsion to birth secretions coating her baby's skin. She was clear that this is what one would expect, it was quite normal, and in no way repulsive. ‘It doesn't cross your mind that you have your chest out and it is covered in mucus because it's your baby at the end of the day’ . Kashir also reflected on cultural aspects of birth, and suggested that blood and bodily fluids on a new baby would cause no cultural challenges to her. ‘He was all wet with blood on him, but he is part of me – just born. He was bound to have blood on him. It's not a problem, not an issue culturally either’ .For Jayne, if the baby had been washed the natural aspect of her birth would have been lost. The time taken to separate and bath her baby would have impacted on how soon she could have held him. ‘I didn't care about the smell of the blood, the feel of him. In fact, I loved it. It made me realise what a beautiful and natural process birth is. I just wanted him, still covered in my blood. I didn't want him washed, I just wanted him’ .Oxytocin, a hormone that has been strongly associated with both mothering and breastfeeding, is released in high levels immediately after the placenta is delivered. Physiologically, this hormone promotes immediate mothering actions, touch, gaze and vocalization. The need of a mother to hold her baby immediately may be influenced by the high levels of this hormone at the time of birth. Oxytocin also reduces the level of free-flowing catecholamines (stress hormones) in the baby . It has Some women referred to their previous birth experiences without SSC. ‘I had thought about it, him being slimy and wet, horrible and messy.’ Lisa went on to explain that ‘In comparison to this birth with immediate SSC, my first birth now appears clinical and cold. He was all washed, clean; there was none of that nice smell about him that you associate with birth. It's that what makes you want to hold them, to get to know them’ (Lisa. English. G2P2. Home birth). Lisa did not experience the ‘messiness’ of birth that she had anticipated and she now ascribed positive associations to SSC. ‘I can't imagine delivering him and twenty minutes later being presented with a pristine baby. I would feel alienated by that, whereas this, a wet, bloodied baby feels like the most natural thing in the world.’In a previous small study , Hannah The women's stories suggest that a mother's caregiving repertoire need not be taught. Indeed, A second Pakistani mother reported that ‘If he had been wet from birth then I wouldn't have minded, wouldn't have been bothered, but blood … It's just the blood I don't like. Other than that you just love your baby’ (Preetia. Pakistani. Caesarean birth). In contrast to Kashir's account, this mother simply had a phobia of blood, which could affect any woman and was not culturally significant. Sakina also did not find birth secretions to be culturally or personally distasteful. She perceived no religious issues about her baby being unwashed or unclean. However, she did explain that the water on the baby made it difficult to hold: a purely practical problem. ‘Not really – it's your blood and gunge, but there is water on the baby, and you're scared it will slip from your hands.’ She reflected on a previous birth: ‘if I had been given a choice, I would have asked them to dry my baby. She was slippery and difficult to hold that was my only problem’ .The women's words suggest that true cultural care must be individualized, without assumptions of universal response with a cultural group. What is welcomed by one mother may be distressing for another, and for many different reasons. These findings contrast sharply with previous suggestions about birth fluids being inevitably associated with cultural abhorrence .The findings from this study offer messages for changes in professional practice, in local policy and in national strategy.The implications for professional practice relate specifically to midwives in this study, but the messages can be seen to be of relevance to other professionals and other fields of practice, too, particularly with regard to being more open to the expressed preferences of service users. The findings demonstrate the potential for erroneous assumption on the part of health professionals, reminding that women from any community, religion or culture may have a phobia of blood or be frightened that a slippery baby may wriggle from their hands. Professional practice must incorporate caution in acting upon unverified assumptions based on cultural background.For the majority of south Asian women in this study , otherwise unacceptable fluids associated with birth were accepted in the specific context of birth. This means that midwives need to consider women's feelings about SSC and birth fluids on an individual basis and be respectful of their wishes. Some women may welcome birth fluids on their babies' skin and view them as a natural part of their birth experience. Other women may prefer secretions to be wiped from their babies' skin, or they may want their babies bathed before SSC begins. Such choices must become routine in the practice of midwives, nurses and other health professionals.This study provides a compelling rationale for changes in labour ward practices to promote environments that enable mothers, babies and fathers to function as a nurturing unit, maximizing the opportunities afforded by hormonal changes at birth, and promoting choices unfettered by cultural stereotyping. For change in practice to occur, health-providing organizations must adopt local policies to ensure that choices are made clear and are available to patients, and they must provide training and leadership in responding in a supportive mode when situations are culturally challenging for service users.Practices that support breastfeeding are embedded into national policy strategies in the UK in order to improve population health and to tackle health inequalities . UNICEF Step 4 of the standards highlights that immediate and continued SSC between the mother and the baby promotes early and instinctive feeding and appears to lead to more confident parenting. However, some maternity units are challenged by step 4. The midwives involved in caring for women in this study were innovative and found ways around this. For example, if the labour ward rooms were busy, they transferred the mother and the baby in SSC to the post-natal wards and continued to keep them together. The midwives' tenacity in supporting mothers' choices demonstrates that the midwives understood the meanings and values that each woman was bringing to her own particular early experience of motherhood.This study provides evidence that SSC is not abhorrent to women from diverse population groups which has been a key issue for implementation of the standards in some UK maternity units where there is a large ethnic population. This study and others, for example, The study was conducted in a single setting, eliciting individual experiences of participants who may not be representative of others in their cultural groups nationally. However, their collective narrative and recordings may find resonance and have implications for midwifery practice in other parts of the world. The need for third-party translation during interviews with Asian women may have added a layer of interpretation to data analysis. The ability of third parties to exclude some groups from participation was underestimated. This occurred through imposition of cultural expectations in the recruitment process by peer group members, a process that was amended once the issue came to light.Stereotypical assumptions about cultural background rather than recognition of women's individual beliefs and needs often characterize professional responses. In this study, once this stereotyping was neutralized, women from all three cultures were seen to enjoy intimate SSC with their newborn babies. This was the case whether they had chosen breastfeeding or bottle-feeding for their babies. This study demonstrates that midwives should take a non-judgemental approach to understanding the choices that women make, particularly when these may not fit into the institutional guidance and protocols.VF: Study conception, data collection. VF and TL: Study design, data analysis, drafting the manuscript. TL: Critical revisions for intellectual content, supervision.


Objective. To establish the percentile charts of birth weights for gestational age and sex within the Cameroonian population. Methods. A review of medical records of infants born between January 2007 and December 2011 at the maternities of two hospitals in Cameroon, Central Africa. Multiple pregnancies, births of HIV infected women, stillbirths, and births with major fetal malformations were excluded. The smooth curves of birth weight for gestational age and sex were created using the Gamlss package under R.3.0.1 software. Results. The birth weights of 12837 live birth singleton infants born to HIV negative women between 28 and 42 weeks of gestation were analyzed to construct the birth weight curves for gestational age and sex. The smoothed percentile curves of birth weights for gestational age and sex of Cameroonian infants have demonstrated an increasing slope until 40 weeks and then a plateau. There was a varied difference of distribution in birth weights for gestational age between Cameroonian, Botswanan, American, and French infants. Conclusion. We established the reference curves of birth weights for gestational age and sex for Cameroonians. The difference in birth weight curves noted between Cameroonian, Botswanan, American, and French infants suggests the importance of establishing the regional birth weight norms. Birth weight is one of the important indicators used to assess the health of an infant at birth. It is often used as an outcome measure in perinatal research or as an indicator of perinatal health in clinical practice . GestatiSmall for gestational age (birth weight < 10th percentile) or large for gestational age (birth weight > 90th percentile) babies may be identified using the centile charts of birth weight for gestational age and sex . For mosIn Cameroon, the reference curves for birth weight used in clinical practice are those established in the European or American populations , 9. The This was a medical record review of infants born between January 2007 and December 2011 at the maternities of the Yaounde General Hospital (YGH) and Yaounde Gyneco-Obstetric and Pediatric Hospital (YGOPH) situated in Cameroon, Central Africa. These hospitals are located in the urban setting of Yaounde and are among the most attended health centers in this town. Yaounde is the political capital of Cameroon; its population is cosmopolitan and representative of all the ethnic groups of this country. Because of their geographical location, the maternities of these two hospitals receive mothers from all ethnic groups of this country. In these maternities, birth records are filled by the midwives.All live born singleton infants from 28 to 42 weeks of gestational age during the study period were recruited. The gestational age was calculated in completed weeks from the last menstrual period since the use of ultrasound in the dating of pregnancies is not a common practice in our milieu. The cases with major congenital abnormalities, stillbirths, HIV positive mothers, unknown and uncertain gestational age, and incomplete data were excluded from the study. Perinatal data was collected from the delivery registries and filled by midwives. This data included date of delivery, gestational age at birth, singleton birth, birth weight, infant sex, viability, stillbirths, infants with major congenital abnormalities observed, and HIV status of the mother.The first step of the statistical analysis consisted in cleaning the outliers from the data. We used the method described by Foster and Kecojevié  who usedThe smoothed percentile curves for the 10th, 25th, 50th, 75th, and 90th percentiles were created using the Gamlss package under R.3.0.1 software. Worm plots and residual plots were used to assess the normality of the curves for each sex   were HIV positive. We excluded the births from HIV positive mothers (303); mothers with unknown HIV status (122); births from multiple pregnancies (264); stillbirths (283); births with major congenital abnormalities (35); births at <28 or >42 weeks of gestational age (129); and births with unknown viability status, birth weight, or gestational age (156). After application of these exclusion criteria, we obtained 12837 live birth singleton infants without congenital abnormalities born to HIV negative women at 28–42 weeks of gestational age. Then, 153 outliers were also excluded leaving a final dataset analysis of 6263 for female infants and 6421 for male infants .P < 0.001). Low birth weight (<2500 g) represented 9.8% of the study population, with 8.3% for male infants and 11.3% for female infants.Crude birth weights for gestational ages ranging from 28 to 42 weeks for male and female infants are illustrated, respectively, in Tables The smoothed percentile curves for the birth weights of male and female Cameroonian infants are represented in This study describes percentile charts of birth weights for gestational age and sex for live singleton infants born in two hospitals in Yaounde. We believe that this hospital based data is representative of the whole Cameroonian population, since the data was collected in two of the most attended hospitals in Yaounde where the population is a mixture of people from different regions of the country. Equally, the proportion of low birth weight infants of 9.8% in this study is close to the 11% of low birth weight infants estimated in the Cameroonian population in 2003 by the UNICEF based on data of demographic and health survey [In most developing countries, the reference of birth weight for gestational age is unavailable. In these countries, there is a lack of national birth weight registers and birth weight is collected via annual demographic health surveys . As a maThe difference in birth weights between Cameroonian born infants and those from Botswana and USA can be explained by the geographical variation due to environmental factors. The small sample size in preterm Cameroonian infants in both sexes and the births from multiple pregnancies included in the Botswana study could skew the data toward the lower birth weights.We noted a difference in the curves of birth weights for gestational age of Cameroonian infants and French infants. The male Cameroonian infants born at <35 weeks tend to have higher birth weights than French born infants at the 10th and 50th percentiles and there after they seem to be less heavy, while the female Cameroonian infants tend to have at the 10th and 50th percentiles a higher birth weight than French female infants. The difference in birth weights for gestational age between Cameroonian and French infants can be explained by racial and geographical factors and probably the smaller sample size of preterm infants in our study. In this study, the sample size was less than 100 between 28 and 34 weeks which did not assure the best statistical strength.One immediate impact of dating pregnancy using the last menstrual period is the misclassification of gestational age with risk of an increase or a decrease in birth weights for gestational age. This inaccuracy of dating pregnancy using the last menstrual period is due to recall bias, varied menstrual cycles, irregular cycles, and misinterpretation of bleeding at the time of embryo implantation . The gesHowever, this study has some limits. Our data was collected from two hospitals in the urban area; thus the rural population was not well represented. Gestational age may be inaccurate when estimated from the last menstrual period. Parity was not taken into consideration when constructing our reference curves. To minimize these errors, we attempted to correct the data by identifying and excluding the outliers.Our study established the birth weight percentile charts for gestational age and sex based on the Cameroonian singleton births. These charts represent the Cameroonian population better than the European or American charts. The differences in curves of birth weights for gestational age observed between the Cameroonian, Botswanan, American, and French populations confirm the geographical variation of birth weights and suggest the importance of establishing the regional birth weight norms. However, there is need to carry out a large multicentric study which will be more representative of the urban and rural populations in our country.


While the association of preterm birth and the risk of maternal cardiovascular disease (CVD) has been well-documented, most studies were limited by the inability to account for smoking during pregnancy – an important risk factor for both preterm birth and CVD. This study aimed to determine whether the increased future risk of maternal cardiovascular disease (CVD) associated with preterm birth is independent of maternal smoking during pregnancy.A population-based record linkage study of 797,056 women who delivered a singleton infant between 1994 and 2011 in New South Wales, Australia was conducted. Birth records were linked to the mothers’ subsequent hospitaliation or death from CVD. Preterm births were categorised as late (35-36 weeks), moderate (33–34 weeks), or extreme (≤32 weeks); and as spontaneous or indicated. Cox proportional hazard regression was used to estimate adjusted hazard ratios (AHR) [95 % CI].During the study period, 59,563 women (7.5 %) had at least one preterm birth. After adjustment for CVD risk factors other than smoking, AHR [95 % CI] of CVD among women who ever had a preterm birth was 1.78 [1.61–1.96]. Associations were greater for extreme (AHR = 1.98 [1.63–2.42]) and moderate (AHR = 2.06 [1.69–2.51]) than late preterm birth (AHR = 1.63 [1.44–1.85]), for indicated (AHR = 2.04 [1.75–2.38]) than spontaneous preterm birth (AHR = 1.65 [1.47–1.86]), and for having ≥ two (AHR = 2.29[1.75–2.99]) than having one preterm birth (AHR = 1.73[1.57–1.92]). A further adjustment for maternal smoking attenuated, but did not eliminate, the associations. Smoking during pregnancy was also independently associated with maternal CVD risks, with associations being stronger for mothers who smoked during last pregnancy (AHR = 2.07 [1.93–2.23]) than mothers who smoked during a prior pregnancy (AHR = 1.64 [1.41–1.90]).Associations of preterm birth and maternal CVD risk are independent of maternal smoking during pregnancy. This underscores the importance of smoking cessation in reducing CVD and suggests that a history of preterm delivery  identifies women who could be targeted for CVD screening and preventative therapies. Preterm birth is a major pregnancy complication affecting 5–18 % of deliveries worldwide . GrowingCigarette smoking is a major modifiable risk factor for both CVD and preterm birth . While tThe current study is based on a cohort of women who had a singleton birth between January 1994 and December 2011 in NSW. With a population of 7 million, NSW is the most populous state in Australia with approximately one third of all Australian births. We excluded women who ever had a pregnancy complicated by chronic or pregnancy hypertension  during the study period, because these conditions are established risk factors for both preterm birth and later life maternal CVD . We alsoFour computerised datasets were linked for the present study: Perinatal Data Collection (PDC) (birth data – from 1994–2011), Admitted Patient Data Collection (APDC) , Registrar of Births, Deaths and Marriages (RBDM) (death data - from January 1994 and December 2011), and Australian Bureau of Statistics (ABS) (cause of death data - from January 1994 and December 2007). The PDC is a statutory surveillance system of all births ≥20 weeks of gestation or ≥ 400 g birth weight in NSW, containing information on maternal characteristics, pregnancy, labour, delivery and infant outcomes that is reported by the attending clinician. APDC is a census of inpatient admissions from all public and private hospitals in NSW. It includes information on patient diagnoses and procedures documented in medical records, and coded according to the Tenth revision of the International Classification of Disease – Australian Modification (ICD10-AM). The RBDM records all deaths in NSW, while the ABS codes the cause of death according to the ICD9 (before 2000) and ICD10-AM (from 2000).Records were linked cross-sectionally  and longitudinally to the mothers’ subsequent hospitalisation or death records to create complete obstetric and medical histories. All linkage was undertaken by the NSW Centre for Health Record Linkage . Probabind trimester ultrasound scans  of CVD among mothers with any preterm birth was 1.78 [1.61 – 1.96]  Table  with no 6] Table , 5 and 6Compared to non-smoking mothers, both crude and adjusted HRs of CVD (and CVD subgroups) among mothers who smoked during last pregnancy were consistently higher than that among mothers who smoked during a prior pregnancy, but not during last pregnancy Table , 6 and 7This study, using linked population-based data, is the first to provide a comprehensive assessment of the relationships between preterm birth and maternal CVD later in life, taking into account the heterogeneity of preterm births. The results indicate that delivery of a preterm infant was associated with a significant increase in the risk of maternal CVD hospitaliation or death in the years following pregnancy. The associations were dose-dependent according to both the severity and number of preterm births and stronger for indicated than for spontaneous preterm birth. Consistent with our hypothesis, the associations were attenuated, but not eliminated, after accounting for maternal smoking during pregnancy. Maternal smoking during pregnancy was also associated with an increased risk of maternal CVD, regardless of whether a woman ever had a preterm birth. In particular, a higher risk estimate was observed in women who smoked during their last pregnancy compared to those who smoked during a pregnancy before the last pregnancy highlighting the benefit of smoking cessation in reducing the risk of subsequent maternal CVD. The observed associations were also independent of the established association between the hypertensive disorders of pregnancy and subsequent maternal CVD , 8.Our observation of a dose-dependent association of preterm birth on maternal CVD risks is well-aligned with previous epidemiological studies. One population-based record linkage study n = 923,686), for example, reported that having a moderate, very, and extreme preterm infant was associated with a 39 %, 157 %, and 128 % increase in the risk of subsequent maternal CVD hospitaliation or death, after accounting for smoking and other CVD risk factors [86, for eIn particular, our study demonstrated a stronger association with maternal CHD for indicated preterm birth. A similar gradient effect has been reported by only one previous study  – strong risk factors for both CVD and preterm birth was excluded. As expected, the increased risk of maternal CVD associated with either preterm birth or maternal smoking was attenuated in the multivariate models. Most previous studies used only preterm birth occurring at the index birth (first birth) to define exposure , 7, 30. A potential weakness of the study relates to the use of multiple datasets that do not cover the same period. There was under-ascertainment of CVD death due to the lack of cause of death data beyond 2007. However, given that only 36 deaths from CVD without prior hospital admission for CVD were identified in the first 8 years (2000 – 2007), we estimated the number of missing deaths from CVD is minimal. Another potential weakness was the delayed commencement of follow up in women who gave birth before 2000. In these women, acute cardiovascular events may have been missed, leading to an underestimate of the incidence of these events and the strength of their association with preterm birth and smoking. However, these shortcomings are not without precedent in population-based studies relying on record linkage data. In one study, for example, the follow-up only started 4–14 years after the index (first) pregnancy . FurtherBased on a large retrospective cohort of women, this study provides robust evidence indicating that the association of preterm birth and future risk of maternal CVD is independent of maternal smoking and hypertensive disorder during pregnancy. This underscores the importance of smoking cessation in reducing CVD and suggests that a history of preterm delivery  can identify a sizeable number of women susceptible to early onset of CVD and premature death in the years following pregnancy. Careful detailing of a woman’s reproductive life including history of preterm birth would enhance assessment of her CVD risk profile, potentially leading to more effective targeting of CVD screening, education and preventative therapies. Furthermore, pregnancy provides an opportunity for lifestyle education to encourage smoking women to quit smoking as well as for indentifying women at elevated risk of subsequent CVD.


Our objThis was a retrospective study of all late preterm neonates during a 1-year period from January 2013. Gestational Age (GA) was calculated as a function of the date of last menstrual period and/or biometrics assigned from the ultrasound measurement of the first trimester. Type of pregnancy (singleton or multiple), use of antepartum steroid therapy, maternal medical disorders, obstetric and/or fetal complications, intrapartum fetal distress, birth weight (BW), gender, Apgar score, need for resuscitation were collected from medical records Rectal temperature was measured in all neonates at birth and at admission to nursery.in utero fetal death. Table 1 was present in Group I in comparison to the others, as well as a higher number of neonates requiring resuscitation, independently of the mode of delivery. In Group II and III, all neonates requiring resuscitation were born by CS. Higher number of neonates with mild hypothermia at admission was detected in Group I. Considerable variations occur in the temperature values in all infants in DR as well as during the transport to the nursery.During the study period there were a total of 3354 births. The number of preterm neonates was 478 14.2%), of these 279 (58%) were late-preterm (249 singleton pregnancy and 30 multiple pregnancy). Three neonates were excluded due to 4.2%, of Late-preterm birth by CS is associated with significant GA-dependent neonatal depression. Additional close monitoring and timely intervention are necessary in the management of these infants in DR.


The effectiveness of transcranial magnetic stimulation (TMS) depends highly on the coil orientation relative to the subject’s head. This implies that the direction of the induced electric field has a large effect on the efficiency of TMS. To improve future protocols, knowledge about the relationship between the coil orientation and the direction of the induced electric field on the one hand, and the head and brain anatomy on the other hand, seems crucial. Therefore, the induced electric field in the cortex as a function of the coil orientation has been examined in this study.The effect of changing the coil orientation on the induced electric field was evaluated for fourteen cortical targets. We used a finite element model to calculate the induced electric fields for thirty-six coil orientations (10 degrees resolution) per target location. The effects on the electric field due to coil rotation, in combination with target site anatomy, have been quantified.The results confirm that the electric field perpendicular to the anterior sulcal wall of the central sulcus is highly susceptible to coil orientation changes and has to be maximized for an optimal stimulation effect of the motor cortex. In order to obtain maximum stimulation effect in areas other than the motor cortex, the electric field perpendicular to the cortical surface in those areas has to be maximized as well. Small orientation changes (10 degrees) do not alter the induced electric field drastically.standard coil orientations, used in cognitive and clinical neuroscience, induce (near) optimal electric fields in the subject-specific head model in most cases.The results suggest that for all cortical targets, maximizing the strength of the electric field perpendicular to the targeted cortical surface area (and inward directed) optimizes the effect of TMS. Orienting the TMS coil based on anatomical information  about the targeted brain area can improve future results. The The online version of this article (doi:10.1186/s12984-015-0036-2) contains supplementary material, which is available to authorized users. Transcranial magnetic stimulation (TMS)  is a non‘standard’ TMS coil orientations, used in several cognitive and clinical neuroscience studies, were considered for our subject-specific volume conduction model.A suitable method to obtain knowledge about the induced field and its direction is volume conduction modeling -14. AlthFor M1 there is already ample evidence for the importance of coil orientation -4,21. Thcortical column cosine model of TMS efficacy (C3-model) [C3-model is supported by volume conduction modeling [The most logical explanation for the coil orientation preference of M1 stimulation is given by the theoretical 3-model) . This mo3-model) ,23 as thmodeling , supportmodeling ,24, and C3-model can possibly contribute in determining the optimal coil orientation for these brain areas and improve experimental TMS studies. If the theoretical model is applicable to M1, it could be argued that it could as well be applicable to other cortical areas, due to the fact that a similar basic columnar structure can be found all over the cerebral cortex [Due to a lack of an outcome measure like the MEP for cortical target areas outside M1, the optimal orientation cannot easily be obtained experimentally. Nevertheless, several brain structures have been studied with TMS in the course of years -10. The l cortex ,23. Thisl cortex . The coil cortex .C3-model is applicable to all cortical areas, we determined the effect of coil orientation for thirteen cortical target locations outside M1 in a realistic head model. From the results, generalizations about coil orientation applicable to all cortical target areas are made to predict the optimal orientations.Based on the premise that the references Table http://www.localite.de) from the subject on whom the head model is based. The coordinates for the three other cortical sites were based on visual inspection of the model. For each cortical target location the coil was rotated systematically in steps of 10 degrees , while keeping the horizontal plane of the TMS coil at the same level and the center at the same location.In order to study the induced electric field in the brain, a highly realistic head model with intricate geometrical tissue boundaries was constructed. Herein, fourteen cortical target locations were selected, including M1  . The con . The coA prerequisite for studying the effect of coil orientation are realistically described tissue boundaries, and especially the boundary between cerebrospinal fluid (CSF) and grey matter (GM), as introduced in the latest models ,14. Sphe3 resolution ) and is based on T1 and T2 magnetic resonance images (MRI) of a healthy 25-year old male subject, with 1 mmFor each combination of cortical target site Table  and coil3ε0 and 105ε0 [0 the permittivity for free space. Previous FEM simulations already demonstrated that permittivity values between 102ε0 and 104ε0 had negligible effects on the distribution of the induced electric field and only permittivity values in the range of 107ε0 had an effect on the electric field distributions [with nd 105ε0 ,29, withibutions .Equation (1) consists of two semi-independent parts. The first part The calculation of geometry ,18. The a on a Mac Pro, 2.66 GHz Quad-Core Intel Xeon with 16 GB memory). To determine the value of Φ throughout the whole volume mesh, four properties were used: 1.) The induced currents follow Ohm’s law , the induced electric field was calculated throughout the whole head model. As we are interested in the TMS induced effects at the cortical level, the fields at the CSF-GM boundary have been visualized. To quantify the effects of coil orientation on the TMS induced field, we used the electric field strength l cortex ,23. The Cortical cosine model and I-waves). Within the target region only the GM elements are used to determine E⊥, because there is evidence that the first neuronal activation by TMS takes place at GM level [E⊥.The target regions, which are used for analysis, are chosen to be spherical (3 mm radius) with their centers located on the cortical surface. By using a fixed radius for each target region, a similar volume is taken for each location. For all targets, except the cerebellar ones, the center of the target region was located in a sulcal wall. They were located in the sulci, because there the field is mostly perpendicular and consequently more likely to be first affected by the stimulation  are shown. The black arrow indicates the direction of the primary electric field directly beneath the coil center (black dot).In Figure red). The highest electric field values are located at the crowns and lips of the gyri, which is in accordance with earlier reports [red and pink).All target locations have multiple gyri with high field amplitudes near the target site  were found in the sulci and almost never on top of the gyri  and outward (blue) directed electric field. The maximum field values for all fourteen target locations and their standard coil orientations, determined over the complete cortical surface, are listed in Table E⊥ are always lower than the maximum values of E⊥ are still between 45 and 80 percent of their corresponding maximum value for The highest field values for the perpendicular component  the standard + 40 degrees, (3) + 90 degrees, (4) + 150 degrees and (5) + 180 degrees of clockwise rotation. The induced electric field strength  are shown. The black arrow again indicates the direction of the primary electric field directly under the coil center (black dot). Both rows in Figure around black dot).In Figure degrees,  + 90 degdegrees,  + 90 degstandard orientation and the 180 degrees rotation of the coil; only the direction of the field reverses from inward to outward (red turns blue and vice versa). The standard orientation induces the strongest E⊥ values directed into the cortex at the anterior sulcal wall of the central sulcus. This is in accordance with earlier findings [The component perpendicular to the cortical surface shows no high field values on top of the gyri, but always inside the sulci . The results again show that for M1, the orientation dependency of the mean field strength is small . However, the standard coil orientation induces almost the highest possible perpendicular electric field, directed into the cortex .The results from Figure l Figure A, especil Figure B. Based It is known from earlier reports that a coil rotation of 90 degrees  will induce the least effective electric field . The resE⊥ within the target region for all thirty-six orientations over the other thirteen cortical surface targets have been calculated. The mean values for the standard coil orientation and the optimal orientation are listed in Table per target location). The results for all other coil orientations can be found in the Additional file E⊥ are determined separately (Table C3-model (E⊥) [Following the same procedure as for M1, the mean values for ly Table . Also fodel (E⊥)  as well,standard orientations found in literature can be considered almost optimal for inducing the strongest perpendicular fields in nearby sulcal walls in our subject-specific model. Only four out of fourteen target locations could possibly be improved with more than 5 percent . A generalization of the results will be discussed in the paragraphs Simulation outside M1 & Generalization. Because of their distinctive results, the cerebellar targets will be discussed separately in more detail in the paragraph Most of the around black dot). The electric field on top of the gyrus is primarily parallel to the cortical surface and never perpendicular. According to the C3-model, the electric field has to be perpendicular and directed into the cortical surface .positive and negative) are produced by a coil orientation of 45 degrees relative to the medial-sagittal plane. A 90-degree coil rotation compared to the optimal orientation, which aligns the figure-of-eight midline with the central sulcus, produces a weak perpendicular component   Figure .standard TMS coil orientations (references Table standard TMS coil orientations are inducing an (near) optimal electric field  and the DLPMC locations (PMR & PML) the choice of orientation was based on physiological outcome measures. For the SMA locations (SM1 & SM2) the choice of orientation was validated by physiological outcome measures. For the other locations the standard TMS coil orientations appear near optimal for the head model used in this study. This could imply that the inter-individual differences in curvature are small enough to not drastically changing the induced electric field . However, the specific results for the locations PMR and PML lessen this statement. Third and lastly, the results show that a coil rotation of 10 degrees  does not change the electric field much  can improve the results of the study. Elaborate computational modeling might not be needed to determine the optimal orientation, although it can provide much information about the induced electric field. Secondly, it can be considered reassuring that the The cortical response to TMS depends on a complex interaction between the applied electric field distribution and the neural elements and networks in the cortex. Herein, the orientation of the electric field is essential, as shown in this study, but also aspects like the type of coil, stimulation  and pulse waveform are important.A generally accepted theory to explain the mechanisms of cortical activation in M1 is based on the generation of the direct (D) and the indirect (I) waves. Stimulation of M1 with a figure-of-eight TMS coil, a monophasic waveform and a posterior-anterior (P-A) field direction, produces several I-waves, reflecting the indirect activation of the layer V pyramidal neurons (P5) . With hiThe P2 and P3 axonal connections to the P5 neurons lie within a cortical column, along the direction of the cortical column axis. This means that an electric field perpendicular to the cortical surface is likely to produce an I1-wave. Because the direction of the induced electric field is predominantly parallel to the plane of the TMS coil, the field in the sulci is mostly perpendicular to the cortical surface. At the top of the gyri the TMS induced electric field is mostly parallel to the cortical surface. This would mean that the I1-wave following TMS stimulation originates in the sulcal wall. The later I-waves are produced by complex circuits, higher stimulation intensities and possibly by other electric field components . This coThe results for stimulation of M1 with a figure-of-eight TMS coil, a monophasic waveform and a P-A field direction are nicely in agreement with the argument stated above. However, there are also other protocols and TMS hardware set-ups. For example, stimulation with a figure-of-eight coil and a biphasic waveform produces less homogeneous descending cortical volleys compared to stimulation with a monophasic waveform ,33. ThisThe above argument is based on the assumption that cortical activation occurs through stimulation of neural elements aligned with the axis of the cortical column. However, this is certainly not the only possible mechanism of cortical activation. For a detailed discussion about the possible mechanisms of cortical activation and neural elements that can be stimulated by TMS, see for example .standard coil orientation for CR and CL stimulation, which induce an electric field with a caudal-rostral direction, cannot be considered optimal. The optimal orientations found in this study would induce a medial-lateral directed field. In addition, the results from Table The results in Table There are two possible explanations for the discrepancies. The first reason could be that the neuronal structures in the cerebellum are quite different with their Purkinje cell population. These cells might be stimulated in a different way and more susceptible to an electric field that is directed parallel to the cerebellar surface. A different reason could be the absence of cerebellar gyri and sulci in this particular model. This is due to the fact that the model is based on 3-Tesla MRI in which the cerebellar gyri are too small to be discerned reliably on the MR images. Therefore, we cannot determine a perpendicular component of the electric field in the sulcal walls of the cerebellum. For future modeling studies that particularly focus on the cerebellum, it would be important to include cerebellar gyri in the model construction process.C3-model is highly suitable to explain the effect of coil orientation on the activation of neuronal populations, but it is still a simplification of the mechanism responsible for the neural activation by TMS. The parallel component of the electric field might also contribute to the activation of neurons in the cortex. As mentioned earlier in the section I-waves and the perpendicular electric field, at higher intensities late I-waves are produced by more complex circuits and possibly other electric field directions [The rections . The notrections . Within The results of this study are also based on assumptions and simplifications about neuronal activation for different cortical areas. The most important ones are the similar mode of neuronal activation and the preferred direction of the electric field for all cortical areas. Nonetheless, the distribution or type of neurons may differ and also the preference of direction for activation by the induced electric field  or with two coil - paired pulse protocols . Such experiments have already been performed, for example for the SMA [The presented FEM simulations are based on well-established laws of physics .