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1.  Infant Temperament is Associated with Potentially Obesogenic Diet at 18 Months 
Objective
This study investigated whether infants’ temperament at 18 months is associated with the feeding of foods and drinks that may increase the risk for later obesity.
Methods
This was a cross-sectional study of mothers and infants (N = 40,266) participating in the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Data were collected by questionnaire. Predictor variables were: infants’ temperament at 18 months (internalizing, externalizing, and surgency/extraversion), and mothers’ negative affectivity. Outcomes variables were feeding of sweet foods, sweet drinks, and night-time caloric drinks at 18 months (all dichotomized). Confounders were child’s gender, weight-for-height at 18 months, breastfeeding, and mother’s level of education.
Results
After controlling for confounders, infant temperament dimensions at 18 months were significantly associated with mothers’ feeding of potentially obesogenic foods and drinks independent of mothers’ negative affectivity. Infants who were more internalizing were more likely to be given sweet foods (OR 1.47, CI 1.32–1.65), sweet drinks (OR 1.76, CI 1.56–1.98), and drinks at night (OR 2.91, CI 2.54–3.33); infants who were more externalizing were more likely to be given sweet food (OR 1.53, CI 1.40–1.67) and sweet drinks (OR 1.22, CI 1.11–1.34); and infants who were more surgent were more likely to be given drinks at night (OR1.66, CI 1.42–1.92).
Conclusions
The association between infant temperament and maternal feeding patterns suggests early mechanisms for later obesity that should be investigated in future studies.
doi:10.3109/17477166.2010.518240
PMCID: PMC3128685  PMID: 20854098
infant temperament; sweet foods; sweet drinks; night-time caloric drinks
2.  Associations Between Temperament at Age 1.5 Years and Obesogenic Diet at Ages 3 and 7 Years 
Objective
To investigate whether temperament in 1.5-year-olds predicts their consumption of potentially obesogenic foods and drinks at ages 3 and 7 years.
Methods
Participants were 6 997 mothers and infants from the Norwegian Mother and Child Cohort Study. Questionnaires were collected during pregnancy, at birth, and at child ages 6 months and 1.5, 3, and 7 years. Predictor variables: children’s temperament at age 1.5 (internalizing, externalizing, surgent) and mothers’ negative affectivity. Outcome variables: children’s consumption of sweet foods, sweet drinks, and fruits/vegetables at ages 3 and 7 (dichotomized at the 85th percentile).
Results
Controlling for covariates, internalizing 1.5-year-olds (anxious, dependent) were 77% and 63% more likely to consume sweet drinks daily at ages 3 and 7, respectively; they were 55% and 43% more likely to consume sweet foods daily at ages 3 and 7, respectively. Externalizing 1.5-year-olds (hyperactive, aggressive) were 34% more likely to consume sweet drinks daily at age 7, 39% and 44% more likely to consume sweet foods daily at ages 3 and 7, respectively, and they were 47% and 33% less likely to consume fruits/vegetables daily at ages 3 and 7, respectively. Surgent 1.5-year-olds (active, sociable) were 197% and 78% more likely to consume two portions of fruits/vegetables daily at ages 3 and 7, respectively. The association of maternal negative affectivity was limited to the child’s consumption of sweet foods at 3 and 7 years.
Conclusion
Early child temperament is a risk factor for obesogenic diet in later childhood. Mechanisms explaining this association need to be explored.
doi:10.1097/DBP.0b013e31826bac0d
PMCID: PMC3492946  PMID: 23117597
child; temperament; obesity; diet; eating
3.  HIV-1 Drug Resistance Emergence among Breastfeeding Infants Born to HIV-Infected Mothers during a Single-Arm Trial of Triple-Antiretroviral Prophylaxis for Prevention of Mother-To-Child Transmission: A Secondary Analysis 
PLoS Medicine  2011;8(3):e1000430.
Analysis of a substudy of the Kisumu breastfeeding trial by Clement Zeh and colleagues reveals the emergence of HIV drug resistance in HIV-positive infants born to HIV-infected mothers treated with antiretroviral drugs.
Background
Nevirapine and lamivudine given to mothers are transmitted to infants via breastfeeding in quantities sufficient to have biologic effects on the virus; this may lead to an increased risk of a breastfed infant's development of resistance to maternal antiretrovirals. The Kisumu Breastfeeding Study (KiBS), a single-arm open-label prevention of mother-to-child HIV transmission (PMTCT) trial, assessed the safety and efficacy of zidovudine, lamivudine, and either nevirapine or nelfinavir given to HIV-infected women from 34 wk gestation through 6 mo of breastfeeding. Here, we present findings from a KiBS trial secondary analysis that evaluated the emergence of maternal ARV-associated resistance among 32 HIV-infected breastfed infants.
Methods and Findings
All infants in the cohort were tested for HIV infection using DNA PCR at multiple study visits during the 24 mo of the study, and plasma RNA viral load for all HIV-PCR–positive infants was evaluated retrospectively. Specimens from mothers and infants with viral load >1,000 copies/ml were tested for HIV drug resistance mutations. Overall, 32 infants were HIV infected by 24 mo of age, and of this group, 24 (75%) infants were HIV infected by 6 mo of age. Of the 24 infants infected by 6 mo, nine were born to mothers on a nelfinavir-based regimen, whereas the remaining 15 were born to mothers on a nevirapine-based regimen. All infants were also given single-dose nevirapine within 48 hours of birth. We detected genotypic resistance mutations in none of eight infants who were HIV-PCR positive by 2 wk of age (specimens from six infants were not amplifiable), for 30% (6/20) at 6 wk, 63% (14/22) positive at 14 wk, and 67% (16/24) at 6 mo post partum. Among the 16 infants with resistance mutations by 6 mo post partum, the common mutations were M184V and K103N, conferring resistance to lamivudine and nevirapine, respectively. Genotypic resistance was detected among 9/9 (100%) and 7/15 (47%) infected infants whose mothers were on nelfinavir and nevirapine, respectively. No mutations were detected among the eight infants infected after the breastfeeding period (age 6 mo).
Conclusions
Emergence of HIV drug resistance mutations in HIV-infected infants occurred between 2 wk and 6 mo post partum, most likely because of exposure to maternal ARV drugs through breast milk. Our findings may impact the choice of regimen for ARV treatment of HIV-infected breastfeeding mothers and their infected infants.
Trial Registration
ClinicalTrials.gov NCT00146380
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Globally, more than 2 million children are infected with the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS), and half a million children are newly infected every year. These infections are mainly the result of mother-to-child transmission (MTCT) of HIV during pregnancy, labor and delivery, or through breastfeeding. MTCT can be greatly reduced by treating HIV-positive mothers and their babies with antiretroviral drugs (ARVs). Without ARVs, up to half of babies born to HIV-positive mothers become infected with HIV. This rate of transmission falls to below 5% if a combination of three ARVs is given to the mother throughout pregnancy. Unfortunately, this triple-ARV therapy is too expensive for use in the resource-limited countries where most MTCT occurs. Instead, many such countries have introduced simpler, shorter ARV regimens such as a daily dose of zidovudine (a nucleoside reverse transcriptase inhibitor or NRTI) given to HIV-positive women during late pregnancy coupled with single-dose nevirapine (a non-nucleoside reverse transcriptase inhibitor or NNRTI) at the onset of labor, zidovudine and lamivudine (another NRTI) during labor and delivery, and single-dose nevirapine given to the baby at birth.
Why Was This Study Done?
More than 95% of HIV-exposed children are born in resource-limited settings where breastfeeding is the norm and is crucial for child survival even though it poses a risk of HIV transmission. Consequently, several recent studies have investigated whether MTCT can be further reduced by giving the mother ARVs while she is breastfeeding. In the Kisumu Breastfeeding Study (KiBS), for example, researchers assessed the effects of giving zidovudine, lamivudine, and either nevirapine or nelfinavir (a protease inhibitor) to HIV-infected women from 34 weeks of pregnancy through 6 months of breastfeeding. The results of KiBS indicate that this approach might be a safe, feasible way to reduce MTCT (see the accompanying paper by Thomas and colleagues). However, low amounts of nevirapine and lamivudine are transferred from mother to infant in breast milk and this exposure to ARVs could induce the development of resistance to ARVs among HIV-infected infants. In this KiBS substudy, the researchers investigate whether HIV drug resistance emerged in any of the HIV-positive infants in the parent study.
What Did the Researchers Do and Find?
In KiBS, 32 infants were HIV-positive at 24 months old; 24 were HIV-positive at 6 months old when their mothers stopped taking ARVs and when breastfeeding was supposed to stop. The researchers analyzed blood samples taken from these infants at various ages and from their mothers for the presence of HIV drug resistance mutations (DNA changes that make HIV resistant to killing by ARVs). They detected no resistance mutations in samples taken from 2-week old HIV-positive infants or from the infants who became infected after the age of 6 months. However, they found resistance mutations in a third and two-thirds of samples taken from 6-week and 6-month old HIV-positive infants, respectively. The commonest mutations conferred resistance to lamivudine and nevirapine. Moreover, resistance mutations were present in samples taken from all the HIV-positive infants whose mothers who had received nelfinavir but in only half those taken from infants whose mothers who had received nevirapine. Finally, most of the mothers of HIV-positive infants had no HIV drug resistance mutations, and only one mother-infant pair had an overlapping pattern of HIV drug resistance mutations.
What Do These Findings Mean?
These findings indicate that, in this KiBS substudy, the emergence of HIV drug resistance mutations in HIV-infected infants whose mothers were receiving ARVs occurred between 2 weeks and 6 months after birth. The pattern of mutations suggests that drug resistance most likely arose through exposure of the infants to low levels of ARVs in breast milk rather than through MTCT of drug-resistant virus. These findings need confirming but suggest that infants exposed to ARVs through breast milk—a situation that may become increasingly common given the reduction in MTCT seen in KiBS and other similar trials—should be carefully monitored for HIV infection. Providers should consider the mothers' regimen when choosing treatment for infants who are found to be HIV-infected despite maternal triple drug prophylaxis. Infants exposed to a maternal regimen with NNRTI drugs should receive first-line therapy with lopinavir/ritonavir, a protease inhibitor. The significance of the NRTI mutations such as M184V with regard to response to therapy needs further evaluation. The M184V mutation may result in hypersensitization to other NRTI drugs and delay or reverse zidovudine resistance. Given the limited availability of alternative drugs for infants in resource-limited settings, provision of the standard WHO-recommended first-line NRTI backbone, which includes 3TC, with enhanced monitoring of the infant to ensure virologic suppression, could be considered. Such an approach should reduce both illness and morbidity among infants who become HIV positive through breastfeeding.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1000430.
The accompanying PLoS Medicine Research article by Thomas and colleagues describes the primary findings of the Kisumu Breastfeeding Study
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on HIV/AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on children, HIV, and AIDS and on preventing mother-to-child transmission of HIV (in English and Spanish)
UNICEF also has information about children and HIV and AIDS (in several languages)
The World Health organization has information on mother-to-child transmission of HIV (in several languages), and guidance on the use of ARVs for preventing MTCT
doi:10.1371/journal.pmed.1000430
PMCID: PMC3066134  PMID: 21468304
4.  Two-Year Morbidity–Mortality and Alternatives to Prolonged Breast-Feeding among Children Born to HIV-Infected Mothers in Côte d'Ivoire 
PLoS Medicine  2007;4(1):e17.
Background
Little is known about the long-term safety of infant feeding interventions aimed at reducing breast milk HIV transmission in Africa.
Methods and Findings
In 2001–2005, HIV-infected pregnant women having received in Abidjan, Côte d'Ivoire, a peripartum antiretroviral prophylaxis were presented antenatally with infant feeding interventions: either artificial feeding, or exclusive breast-feeding and then early cessation from 4 mo of age. Nutritional counseling and clinical management were provided for 2 y. Breast-milk substitutes were provided for free. The primary outcome was the occurrence of adverse health outcomes in children, defined as validated morbid events (diarrhea, acute respiratory infections, or malnutrition) or severe events (hospitalization or death). Hazards ratios to compare formula-fed versus short-term breast-fed (reference) children were adjusted for confounders (baseline covariates and pediatric HIV status as a time-dependant covariate). The 18-mo mortality rates were also compared to those observed in the Ditrame historical trial, which was conducted at the same sites in 1995–1998, and in which long-term breast-feeding was practiced in the absence of any specific infant feeding intervention. Of the 557 live-born children, 262 (47%) were breast-fed for a median of 4 mo, whereas 295 were formula-fed. Over the 2-y follow-up period, 37% of the formula-fed and 34% of the short-term breast-fed children remained free from any adverse health outcome (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI], 0.87–1.38; p = 0.43). The 2-y probability of presenting with a severe event was the same among formula-fed (14%) and short-term breast-fed children (15%) (adjusted HR, 1.19; 95% CI, 0.75–1.91; p = 0.44). An overall 18-mo probability of survival of 96% was observed among both HIV-uninfected short-term and formula-fed children, which was similar to the 95% probability observed in the long-term breast-fed ones of the Ditrame trial.
Conclusions
The 2-y rates of adverse health outcomes were similar among short-term breast-fed and formula-fed children. Mortality rates did not differ significantly between these two groups and, after adjustment for pediatric HIV status, were similar to those observed among long-term breast-fed children. Given appropriate nutritional counseling and care, access to clean water, and a supply of breast-milk substitutes, these alternatives to prolonged breast-feeding can be safe interventions to prevent mother-to-child transmission of HIV in urban African settings.
Given appropriate nutritional counseling and care, access to clean water, and supply of breast milk substitutes, replacing prolonged breast-feeding with formula-feeding appears to be a safe intervention to prevent mother-to-child transmission of HIV in this setting.
Editors' Summary
Background.
The HIV virus can be transmitted from infected mothers to their babies during pregnancy and birth as well as after birth through breast milk. Mother-to-child transmission in developed countries has been all but eliminated by treatment of mothers with the best available combination of antiretroviral drugs and by asking them to avoid breast-feeding. However, in many developing countries, the best drug treatments are not available to mothers. Moreover, breast-feeding is generally the best nutritional choice for infants, especially in areas where resources such as clean water, formula feed, and provision of healthcare are scarce. And even if formula feed is available, formula-fed babies might be at higher risk of dying from diarrhea and chest infections, which are more common in infants who are not breast-fed. International guidelines say that HIV-positive mothers should avoid all breast-feeding and adopt formula feeding instead if this option is practical and safe for them, which would require that they can afford formula feed and have easy access to clean water. If formula-feeding is not feasible, guidelines recommend that mothers should breast-feed only for the first few months and then stop and switch the baby to solid food. One of these two alternative options should be feasible in most African cities if mothers are given the right support.
Why Was This Study Done?
Several completed and ongoing studies are assessing the relative risks and benefits of the two recommended strategies for different developing country locations, and this is one of them. The study, the “Ditrame Plus” trial by researchers from France and Côte d'Ivoire, was conducted in Abidjan, an urban West African setting. The goal was to compare death rates and rates of certain diseases (such as diarrhea and chest infections) between babies born to HIV-positive mothers that were formula-fed and those that were breast-fed for a short time after birth.
What Did the Researchers Do and Find?
HIV-positive pregnant women were invited to enter the study, and they received short-term drug treatments intended to reduce the risk of HIV transmission to their babies. Women in the trial were then asked to choose one of the two feeding options and offered support and counseling for either one. This support included free formula, transport, and healthcare provision. Babies were followed up to their second birthday, and data were collected on death rates and any serious illnesses. A total of 643 women were enrolled into the study, and safety data were collected for 557 babies, of whom 295 were in the formula group and 262 were in the short-term breast-feeding group. The researchers corrected for HIV infection in the babies and found no evidence that the risk of other negative health outcomes and death rates was any different between the formula-fed babies and short-term breast-fed babies. Looking specifically at individual diseases, the researchers found that the risks for diarrhea and chest infections were slightly higher among formula-fed babies, but this did not translate into a greater risk of death or worse overall health. They also compared the death rates in this study with some historical data from a previous research project done in the same area on children born to HIV-positive mothers who had practiced long-term breast-feeding. The mother-to-child transmission rate of HIV had been much higher in that earlier trial, but looking only at the HIV-negative children, the researchers found no difference in risk for death or serious disease between the formula-fed or short-term breast-fed babies from the Ditrame Plus trial and the long-term breast-fed babies from the earlier trial.
What Do These Findings Mean?
This study shows that if HIV-positive mothers are well supported, either of the two feeding options currently recommended (formula-only feed, or short-term breast-feeding) are likely to be equivalent in terms of the baby's chances for survival and health. However, women in this study were offered a great deal of support and the findings may not necessarily apply to real-life situations in other settings in Africa, or outside the context of a research project. In addition to routine care after birth, access to better drugs to prevent mother-to-child transmission in developing countries remains an important goal.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/doi:10.1371/journal.pmed.0040017.
Resources from Avert (an AIDS charity) on HIV and infant feeding.
Information from the US Centers for Disease Control on mother-to-child transmission of HIV
Guidelines from the World Health Organization on mother-to-child transmission of HIV
AIDSMap pages on breast-feeding and HIV
HIV Care and PMTCT in Resource-Limited Setting contains monthly bulletins and a database devoted to HIV/AIDS infections and prevention of the mother-to-child transmission of HIV
The Ghent group is a network of researchers and policymakers in the area of prevention of mother-to-child transmission of HIV
doi:10.1371/journal.pmed.0040017
PMCID: PMC1769413  PMID: 17227132
5.  HIV: prevention of mother-to-child transmission  
BMJ Clinical Evidence  2011;2011:0909.
Introduction
Over 2 million children are thought to be living with HIV/AIDS worldwide, of whom over 80% live in sub-Saharan Africa. Without antiretroviral treatment, the risk of HIV transmission from infected mothers to their children is 15% to 30% during gestation or labour, with an additional transmission risk of 10% to 20% associated with prolonged breastfeeding. HIV-1 infection accounts for most infections; HIV-2 is rarely transmitted from mother to child. Transmission is more likely in mothers with high viral loads, advanced disease, or both, in the presence of other sexually transmitted diseases, and with increased exposure to maternal blood. Mixed feeding practices (breast milk plus other liquids or solids) and prolonged breastfeeding are also associated with increased risk of mother-to-child transmission of HIV.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of measures to reduce mother-to-child transmission of HIV? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed a GRADE evaluation of the quality of evidence for interventions.
Results
We found 53 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiretroviral drugs, different methods of infant feeding, elective caesarean section, immunotherapy, micronutrient supplements, vaginal microbicides, and vitamin supplements.
Key Points
Without active intervention, the risk of mother-to-child transmission (MTCT) of HIV-1 is high, especially in populations where prolonged breastfeeding is the norm. Without antiviral treatment, the risk of transmission of HIV from infected mothers to their children is approximately 15% to 30% during pregnancy and labour, with an additional transmission risk of 10% to 20% associated with prolonged breastfeeding.HIV-2 is rarely transmitted from mother to child.Transmission is more likely in mothers with high viral loads, advanced HIV disease, or both.Without antiretroviral treatment (ART), 15% to 35% of vertically infected infants die within the first year of life.The long-term treatment of children with ART is complicated by multiple concerns regarding the complications associated with life-long treatment, including adverse effects of antiretroviral drugs, difficulties of adherence across the developmental trajectory of childhood and adolescence, and the development of resistance.From a paediatric perspective, successful prevention of MTCT and HIV-free survival for infants remain the most important focus.
Antiretroviral drugs given to the mother during pregnancy or labour, to the baby immediately after birth, or to the mother and baby reduce the risk of intrauterine and intrapartum MTCT of HIV-1 and when given to the infant after birth and to the mother or infant during breastfeeding reduce the risk of postpartum MTCT of HIV-1.
Reductions in MTCT are possible using multidrug ART regimens. Longer courses of ART are more effective, but the greatest benefit is derived from treatment during late pregnancy, labour, and early infancy.Suppression of the maternal viral load to undetectable levels (below 50 copies/mL) using highly active antiretroviral therapy (HAART) offers the greatest risk reduction, and is currently the standard of care offered in most resource-rich countries, where MTCT rates have been reduced to 1% to 2%. Alternative short-course regimens have been tested in resource-limited settings where HAART is not yet widely available. There is evidence that short courses of antiretroviral drugs have confirmed efficacy for reducing MTCT. Identifying optimal short-course regimens (drug combination, timing, and cost effectiveness) for various settings remains a focus for ongoing research.The development of viral resistance in mothers and infants after single-dose nevirapine and other short-course regimens that include single-dose nevirapine is of concern. An additional short-course of antiretrovirals with a different regimen during labour and early postpartum, and the use of HAART, may decrease the risk of viral resistance in mothers, and in infants who become HIV-infected despite prophylaxis.World Health Organization guidelines recommend starting prophylaxis with antiretroviral drugs from as early as 14 weeks' gestation, or as soon as possible if women present late in pregnancy, in labour, or at delivery.
Elective caesarean section at 38 weeks may reduce vertical transmission rates (apart from breast-milk transmission). The potential benefits of this intervention need to be balanced against the increased risk of surgery-associated complications, high cost, and feasibility issues. These reservations are particularly relevant in resource-limited settings.
Immunotherapy with HIV hyperimmune globulin seems no more effective than immunoglobulin without HIV antibody at reducing HIV-1 MTCT risk.
Vaginal microbicides have not been demonstrated to reduce HIV-1 MTCT risk.
There is no evidence that supplementation with vitamin A reduces the risk of HIV-1 MTCT, and there is concern that postnatal vitamin A supplementation for mother and infant may be associated with increased risk of mortality.
We don't know whether micronutrients are effective in prevention of MTCT of HIV as we found no RCT evidence on this outcome.
Avoidance of breastfeeding prevents postpartum transmission of HIV, but formula feeding requires access to clean water and health education. The risk of breastfeeding-related HIV transmission needs to be balanced against the multiple benefits that breastfeeding offers. In resource-poor countries, breastfeeding is strongly associated with reduced infant morbidity and improved child survival. Exclusive breastfeeding during the first 6 months may reduce the risk of HIV transmission compared with mixed feeding, while retaining most of its associated benefits.In a population where prolonged breastfeeding is usual, early, abrupt weaning may not reduce MTCT or HIV-free survival at 2 years compared with prolonged breastfeeding, and may be associated with a higher rate of infant mortality for those infants diagnosed as HIV-infected at <4 months of age. Antiretrovirals given to the mother or the infant during breastfeeding can reduce the risk of HIV transmission in the postpartum period. World Health Organization guidelines recommend that HIV-positive mothers should exclusively breastfeed for the first 6 months, after which time appropriate complementary foods can be introduced. Breastfeeding should be continued for the first 12 months of the infant's life, and stopped only when an adequate diet without breast milk can be provided. Heat- or microbicidal-treated expressed breast milk may offer value in particular settings.
PMCID: PMC3217724  PMID: 21477392
6.  Pregnancy and Infant Outcomes among HIV-Infected Women Taking Long-Term ART with and without Tenofovir in the DART Trial 
PLoS Medicine  2012;9(5):e1001217.
Diana Gibb and colleagues investigate the effect of in utero tenofovir exposure by analyzing the pregnancy and infant outcomes of HIV-infected women enrolled in the DART trial.
Background
Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)–recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure.
Methods and Findings
Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models.
382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0–4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (<22 wk). Of 226 live-births, seven (3%) infants died <2 wk from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero tenofovir exposure (p>0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12–38) months. From mothers' ART, 62/9/111 infants had no/20%–89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75–212) days. Overall, 14 infants died at median (IQR) age 9 (3–23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14 children with no effect of in utero tenofovir (p>0.1). There was no evidence that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height- and weight for age were similar to general (HIV-uninfected) Ugandan populations. Study limitations included relatively small size and lack of randomisation to maternal ART regimens.
Conclusions
Overall 1-year 5% infant mortality was similar to the 2%–4% post-neonatal mortality observed in this region. No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure. Although some infants died untested, absence of recorded HIV infection with combination ART in pregnancy is encouraging. Detailed safety of tenofovir for pre-exposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children.
Trial registration
www.controlled-trials.com ISRCTN13968779
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Currently, about 34 million people (mostly in low- and middle-income countries) are infected with HIV, the virus that causes AIDS. At the beginning of the epidemic, more men than women were infected with HIV but now about half of all people living with HIV/AIDS are women, most of who became infected through unprotected sex with an infected partner. In sub-Saharan Africa alone, 12 million women are HIV-positive. Worldwide, HIV/AIDS is the leading cause of death among women of child-bearing age. Moreover, most of the 400,000 children who become infected with HIV every year acquire the virus from their mother during pregnancy or birth, or through breastfeeding, so-called mother-to-child transmission (MTCT). Combination antiretroviral therapy (ART)—treatment with cocktails of powerful antiretroviral drugs—reduces HIV-related illness and death among women, and ART given to HIV-positive mothers during pregnancy and delivery and to their newborn babies greatly reduces MTCT.
Why Was This Study Done?
Because of ongoing international efforts to increase ART coverage, more HIV-positive women in Africa have access to ART now than ever before. However, little is known about pregnancy outcomes among HIV-infected African women taking ART throughout pregnancy for their own health or about the long-term outcomes of their offspring. In particular, few studies have examined the effect of taking tenofovir (an antiretroviral drug that is now recommended as part of first-line ART) throughout pregnancy. Tenofovir readily crosses from mother to child during pregnancy and, in animal experiments, high doses of tenofovir given during pregnancy caused bone demineralization (which weakens bones), kidney problems, and impaired growth among offspring. In this study, the researchers analyze data collected on pregnancy and infant outcomes among Ugandan and Zimbabwean HIV-positive women who took ART throughout pregnancy in the Development of AntiRetroviral Therapy in Africa (DART) trial. This trial was designed to test whether ART could be safely and effectively delivered in Africa without access to the expensive laboratory tests that are routinely used to monitor ART toxicity and efficacy in developed countries.
What Did the Researchers Do and Find?
The pregnancy outcomes of 302 women who became pregnant during the DART trial and information on birth defects among their babies were collected as part of the DART protocol; information on the survival, growth, and development of the infants born to these women was collected in a separate infant study. Most of the women who became pregnant were taking tenofovir-containing ART before and throughout their pregnancies. 58% of the pregnancies resulted in a live birth, 7% resulted in a stillbirth (birth of a dead baby at any time from 22 weeks gestation to the end of pregnancy), and 35% resulted in a termination or miscarriage (before 22 weeks gestation). Of the 226 live births, seven infants died within 2 weeks and seven had birth defects. Similar proportions of the infants exposed and not exposed to tenofovir during pregnancy died soon after birth or had birth defects. Of the 182 surviving infants who were enrolled in the infant study, 14 subsequently died at an average age of 9 months, giving a 1-year mortality of 5%. None of the surviving children who were tested (172 infants) were HIV infected. No bone fractures or major kidney problems occurred during follow-up and prebirth exposure to tenofovir in utero had no effect on growth or weight gain at 2 years (in contrast to a previous US study).
What Do These Findings Mean?
By showing that prebirth tenofovir exposure does not affect pregnancy outcomes or increase birth defects, growth abnormalities, or kidney problems, these findings support the use of tenofovir-containing ART during pregnancy among HIV-positive African women, and suggest that it could also be used to prevent women of child-bearing age acquiring HIV-infection heterosexually. Notably, the observed 5% 1-year infant mortality is similar to the 2%–4% infant mortality normally seen in the region. The absence of HIV infection among the infants born to the DART participants is also encouraging. However, this is a small study (only 111 infants were exposed to tenofovir throughout pregnancy) and women were not randomly assigned to receive tenofovir-containing ART. Consequently, more studies are needed to confirm that tenofovir exposure during pregnancy does not affect pregnancy outcomes or have any long-term effects on infants. Such studies are essential because the use of tenofovir as a treatment for women who are HIV-positive is likely to increase and tenofovir may also be used in the future to prevent HIV acquisition in HIV-uninfected women.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001217.
Information is available from the US National Institute of Allergy and infectious diseases on all aspects of HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment (in several languages)
Information is available from Avert, an international AIDS nonprofit on many aspects of HIV/AIDS, including detailed information on HIV/AIDS treatment and care, women, HIV and AIDS, children, HIV and AIDS, and on HIV/AIDS and pregnancy (some information in English and Spanish); personal stories of women living with HIV are available
More information about the DART trial is available
Additional patient stories about living with HIV/AIDS are available through the nonprofit website Healthtalkonline
doi:10.1371/journal.pmed.1001217
PMCID: PMC3352861  PMID: 22615543
7.  Association of Breastfeeding With Maternal Control of Infant Feeding at Age 1 Year 
Pediatrics  2004;114(5):e577-e583.
Objective
Previous studies have found that breastfeeding may protect infants against future overweight. One proposed mechanism is that breastfeeding, compared with bottle-feeding, may promote maternal feeding styles that are less controlling and more responsive to infant cues of hunger and satiety, thereby allowing infants greater self-regulation of energy intake. The objective of this study was to examine whether preponderance of breastfeeding in the first 6 months of life and breastfeeding duration are associated with less maternal restrictive behavior and less pressure to eat.
Methods
We studied 1160 mother–infant pairs in Project Viva, an ongoing prospective cohort study of pregnant mothers and their children. The main outcome measures were mothers’ reports of restricting their children’s food intake and of pressuring their children to eat more food, as measured by a modified Child Feeding Questionnaire (CFQ) at 1 year postpartum. Restriction was defined by strongly agreeing or agreeing with the following question from the modified CFQ: “I have to be careful not to feed my child too much.” We derived a continuous pressure to eat score from 5 questions of the modified CFQ. We used multiple logistic regression to examine the association between preponderance of breastfeeding in the first 6 months of life, breastfeeding duration, and mothers’ restriction of children’s access to food. We used multiple linear regression, both before and after adjusting for several groups of confounders, to predict the effects of breastfeeding on the mothers’ scores for pressuring their children to eat.
Results
The mean (SD) age of the women was 32.4 (4.8) years; 24% of the women were nonwhite, and 32% were primigravidas. At 6 months postpartum, 24% of the mothers were exclusively breastfeeding, 25% were mixed feeding, 41% had weaned, and 10% had fed their infants formula only. The mean (SD) duration of breastfeeding was 6.3 (4.5) months. Thirteen percent of the mothers strongly agreed or agreed with the restriction question. The mean (SD) score on the pressure to eat scale was 5.3 (3.7), and the range was 0 to 20. After adjusting for mothers’ preexisting concerns about their children’s future eating and weight status, as well as sociodemographic, economic, and anthropometric predictors of breastfeeding duration, we found that the longer the mothers breastfed, the less likely they were to restrict their children’s food intake at age 1 year. The adjusted odds ratio was 0.89 (95% confidence interval [CI]: 0.84–0.95) for each 1-month increment in breastfeeding duration. In addition, we found that compared with mothers who were exclusively formula feeding, mothers who were exclusively breastfeeding at 6 months of age had much lower odds of restricting their children’s food intake at 1 year (odds ratio: 0.27; 95% CI: 0.10–0.72). Preponderance of breastfeeding in the first 6 months of life and breastfeeding duration (β = −0.01 points on the 0–20 scale for each additional 1 month of breastfeeding [95% CI: −0.07 to 0.05]) were not related to mothers’ pressuring their children to eat more.
Conclusion
Mothers who fed their infants breast milk in early infancy and who breastfed for longer periods reported less restrictive behavior regarding child feeding at 1 year. Additional longitudinal studies should examine the extent to which any protective effect of breastfeeding on overweight is explained by decreased maternal feeding restriction.
doi:10.1542/peds.2004-0801
PMCID: PMC1989686  PMID: 15492358
8.  Task-Oriented and Bottle Feeding Adversely Affect the Quality of Mother-Infant Interactions Following Abnormal Newborn Screens 
Objective
Examine effects of newborn screening (NBS) and neonatal diagnosis on the quality of mother-infant interactions in the context of feeding.
Methods
Study compared the quality of mother-infant feeding interactions among four groups of infants classified by severity of NBS and diagnostic results: cystic fibrosis (CF), congenital hypothyroidism, heterozygote CF carrier, and healthy with normal NBS. The Parent-Child Early Relational Assessment and a task-oriented item measured the quality of feeding interactions for 130 dyads, infant ages 3–19 weeks (M=9.19, SD=3.28). The Center for Epidemiologic Studies Depression Scale and State-Trait Anxiety Inventory measured maternal depression and anxiety.
Results
Composite Indicator Structure Equation Modeling showed that infant diagnostic status and, to a lesser extent, maternal education predicted feeding method. Mothers of infants with CF were most likely to bottle feed, which was associated with more task-oriented maternal behavior than breastfeeding. Mothers with low task-oriented behavior showed more sensitivity and responsiveness to infant cues, as well as less negative affect and behavior in their interactions with their infants than mothers with high task-oriented scores. Mothers of infants with CF were significantly more likely to have clinically significant anxiety and depression than the other groups. However, maternal psychological profile did not predict feeding method or interaction quality.
Conclusions
Mothers in the CF group were the least likely to breastfeed. Research is needed to explicate long-term effects of feeding methods on quality of mother-child relationship and ways to promote continued breastfeeding following a neonatal CF diagnosis.
doi:10.1097/DBP.0b013e3181dd5049
PMCID: PMC2946358  PMID: 20495477
9.  Genetic testing of newborns for type 1 diabetes susceptibility: a prospective cohort study on effects on maternal mental health 
BMC Medical Genetics  2010;11:112.
Background
Concerns about the general psychological impact of genetic testing have been raised. In the Environmental Triggers of Type 1 Diabetes (MIDIA) study, genetic testing was performed for HLA-conferred type 1 diabetes susceptibility among Norwegian newborns. The present study assessed whether mothers of children who test positively suffer from poorer mental health and well-being after receiving genetic risk information about their children.
Methods
The study was based on questionnaire data from the Norwegian Mother and Child Cohort (MoBa) study conducted by the Norwegian Institute of Public Health. Many of the mothers in the MoBa study also took part in the MIDIA study, in which their newborn children were tested for HLA-conferred genetic susceptibility for type 1 diabetes. We used MoBa questionnaire data from the 30th week of pregnancy (baseline) and 6 months post-partum (3-3.5 months after disclosure of test results). We measured maternal symptoms of anxiety and depression (SCL-8), maternal self-esteem (RSES), and satisfaction with life (SWLS). The mothers also reported whether they were seriously worried about their child 6 months post-partum. We compared questionnaire data from mothers who had received information about having a newborn with high genetic risk for type 1 diabetes (N = 166) with data from mothers who were informed that their baby did not have a high-risk genotype (N = 7224). The association between genetic risk information and maternal mental health was analysed using multiple linear regression analysis, controlling for baseline mental health scores.
Results
Information on genetic risk in newborns was found to have no significant impact on maternal symptoms of anxiety and depression (p = 0.9), self-esteem (p = 0.2), satisfaction with life (p = 0.2), or serious worry about their child (OR = 0.98, 95% CI 0.64-1.48). Mental health before birth was strongly associated with mental health after birth. In addition, an increased risk of maternal worry was found if the mother herself had type 1 diabetes (OR = 2.39, 95% CI 1.2-4.78).
Conclusions
This study did not find evidence supporting the notion that genetic risk information about newborns has a negative impact on the mental health of Norwegian mothers.
doi:10.1186/1471-2350-11-112
PMCID: PMC3152763  PMID: 20630116
10.  Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis 
PLoS Medicine  2015;12(8):e1001865.
Background
Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach.
Methods and Findings
We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 × 10−9), birth weight (p = 2.19 × 10−15), and gestational age (p = 1.51 × 10−7). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in ~0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects.
Conclusions
Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring.
Using a Mendelian randomization approach, Ge Zhang and colleagues examine the causal relationship between maternal height, birth size, and gestational age at birth.
Editors' Summary
Background
Soon after the birth of a baby, doting parents send messages to friends and relatives or post information on social media sites to let everyone know when their new baby boy or girl was born. They may also post information about how heavy he/she was at birth and his/her length. These pregnancy outcomes, together with gestational age at birth (the length of time that a baby has spent developing in its mother’s womb), affect the baby’s immediate health and survival. Importantly, however, these pregnancy outcomes are also associated with the risk of long-term adverse health outcomes such as obesity, cardiometabolic disorders (heart disease and conditions such as diabetes that affect how the body makes energy from food), and neuropsychiatric conditions (mental disorders attributable to diseases of the nervous system, such as depression). For example, some studies have shown an association between low birth weight and an increased risk of type 2 diabetes later in life.
Why Was This Study Done?
Identification of the environmental and genetic factors that causally influence gestational age, length, and weight at birth would improve our understanding of why these pregnancy outcomes are associated with disease during adulthood and could help in the design of strategies to prevent these diseases. Epidemiological studies (investigations that examine disease patterns in populations) suggest that, compared to tall mothers, short mothers tend to deliver their babies at earlier gestational ages, with lower birth weights and lengths. Epidemiological studies cannot show, however, whether variations in maternal height cause variations in pregnancy outcomes. Other characteristics shared by tall mothers might actually determine the size and gestational age of their offspring (confounding). Here, the researchers use “Mendelian randomization” to assess the causal effect of maternal height on the size and gestational age at birth of babies. Because gene variants are inherited randomly, they are not prone to confounding. So, if maternal height actually affects gestational age and size at birth, genetic variants (instruments) that affect maternal height should be associated with differences in gestational age and size at birth, provided confounding due to the transmission of parental alleles (variant forms of genes; people have two alleles of every gene, one inherited from each parent) is avoided by adjusting for the baby’s genotype.
What Did the Researchers Do and Find?
The researchers used phenotype data (observable characteristics such as maternal height and birth weight of the baby) and single nucleotide polymorphism (SNP; a type of genetic variant) data obtained from 3,486 Nordic mother/baby pairs. Analysis of the phenotype data indicated that maternal height was significantly associated with length, weight, and gestational age at birth (a significant association is unlikely to have arisen by chance). For their Mendelian randomization analysis, the researchers constructed a genetic score based on 697 SNPs known to be associated with adult height. To avoid confounding due to genetic sharing between the mother and baby, they determined which of the height-associated alleles each baby had inherited from its mother and used the nontransmitted haplotype score as a genetic instrument for maternal height (a haplotype is a set of DNA variations that are inherited together). Birth length and weight were significantly associated with both the maternal and paternal transmitted haplotype scores but not with the maternal nontransmitted haplotype score. However, gestational age was significantly but modestly associated with the maternal nontransmitted haplotype score.
What Do These Findings Mean?
The validity of the assumptions that underlie the Mendelian randomization approach and the design of the studies supplying the data for this analysis may affect the accuracy of the findings reported here. Nevertheless, these findings suggest that the observed association between maternal height and fetal growth measurements is mainly determined by the genetics of the baby. That is, differences in maternal height do not cause differences in birth weight or length. Rather, some of the gene variants that the baby inherits from its mother determine both its size and its mother’s height. These findings also provide weak evidence that the association between maternal height and gestational age is causal. Maternal height might, for example, causally influence gestational age by limiting the space available for the baby’s growth before birth. Finally, these findings introduce an extension to the Mendelian randomization approach that can be used to investigate causal associations between parental characteristics and offspring outcomes.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001865.
The March of Dimes, a not-for-profit organization for pregnancy and baby health, provides information about low birth weight and its consequences
Nemours, a not-for-profit organization for child health, provides information about the weight of newborn babies (in English and Spanish)
Wikipedia has pages on birth weight, gestational age, and Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
MedlinePlus provides information and links to additional resources about birth weight and a brief explanation of gestational age (in English and Spanish)
doi:10.1371/journal.pmed.1001865
PMCID: PMC4540580  PMID: 26284790
11.  The NOURISH randomised control trial: Positive feeding practices and food preferences in early childhood - a primary prevention program for childhood obesity 
BMC Public Health  2009;9:387.
Background
Primary prevention of childhood overweight is an international priority. In Australia 20-25% of 2-8 year olds are already overweight. These children are at substantially increased the risk of becoming overweight adults, with attendant increased risk of morbidity and mortality. Early feeding practices determine infant exposure to food (type, amount, frequency) and include responses (eg coercion) to infant feeding behaviour (eg. food refusal). There is correlational evidence linking parenting style and early feeding practices to child eating behaviour and weight status. A focus on early feeding is consistent with the national focus on early childhood as the foundation for life-long health and well being. The NOURISH trial aims to implement and evaluate a community-based intervention to promote early feeding practices that will foster healthy food preferences and intake and preserve the innate capacity to self-regulate food intake in young children.
Methods/Design
This randomised controlled trial (RCT) aims to recruit 820 first-time mothers and their healthy term infants. A consecutive sample of eligible mothers will be approached postnatally at major maternity hospitals in Brisbane and Adelaide. Initial consent will be for re-contact for full enrolment when the infants are 4-7 months old. Individual mother- infant dyads will be randomised to usual care or the intervention. The intervention will provide anticipatory guidance via two modules of six fortnightly parent education and peer support group sessions, each followed by six months of regular maintenance contact. The modules will commence when the infants are aged 4-7 and 13-16 months to coincide with establishment of solid feeding, and autonomy and independence, respectively. Outcome measures will be assessed at baseline, with follow up at nine and 18 months. These will include infant intake (type and amount of foods), food preferences, feeding behaviour and growth and self-reported maternal feeding practices and parenting practices and efficacy. Covariates will include sociodemographics, infant feeding mode and temperament, maternal weight status and weight concern and child care exposure.
Discussion
Despite the strong rationale to focus on parents' early feeding practices as a key determinant of child food preferences, intake and self-regulatory capacity, prospective longitudinal and intervention studies are rare. This trial will be amongst to provide Level II evidence regarding the impact of an intervention (commencing prior to age 12 months) on children's eating patterns and behaviours.
Trial Registration
ACTRN12608000056392
doi:10.1186/1471-2458-9-387
PMCID: PMC2770488  PMID: 19825193
12.  Human Papillomavirus (HPV) infection in pregnant women and mother-to-child transmission of genital HPV genotypes: a prospective study in Spain 
Background
Studies on HPV infection in pregnant women and HPV transmission to the child have yielded inconsistent results.
Methods
To estimate mother-to-child HPV transmission we carried out a prospective cohort study that included 66 HPV-positive and 77 HPV-negative pregnant women and their offspring attending a maternity hospital in Barcelona. To estimate HPV prevalence and genotype distribution in pregnancy we also carried out a related screening survey of cervical HPV-DNA detection among 828 pregnant women. Cervical cells from the mother were collected at pregnancy (mean of 31 weeks) and at the 6-week post-partum visit. Exfoliated cells from the mouth and external genitalia of the infants were collected around birth, at the 6-week post-partum visit, and around 3, 6, 12, and 24 months of age. All samples were tested for HPV using PCR. Associations between potential determinants of HPV infection in pregnant women and of HPV positivity in infants were also explored by logistic regression modelling.
Results
Overall cervical HPV-DNA detection in pregnant women recruited in the HPV screening survey was 6.5% (54/828). Sexual behavior-related variables, previous histories of genital warts or sexually transmitted infections, and presence of cytological abnormalities were statistically significantly and positively associated with HPV DNA detection in pregnant women recruited in the cohort. At 418 infant visits and a mean follow-up time of 14 months, 19.7% of infants born to HPV-positive mothers and 16.9% of those born to HPV-negative mothers tested HPV positive at some point during infants' follow-up. The most frequently detected genotype both in infants and mothers was HPV-16, after excluding untyped HPV infections. We found a strong and statistically significant association between mother's and child's HPV status at the 6-week post-partum visit. Thus, children of mothers' who were HPV-positive at the post-partum visit were about 5 times more likely to test HPV-positive than children of corresponding HPV-negative mothers (p = 0.02).
Conclusion
This study confirms that the risk of vertical transmission of HPV genotypes is relatively low. HPV persistence in infants is a rare event. These data also indicate that vertical transmission may not be the sole source of HPV infections in infants and provides partial evidence for horizontal mother-to-child HPV transmission.
doi:10.1186/1471-2334-9-74
PMCID: PMC2696457  PMID: 19473489
13.  Children and Eating: Personality and Gender are Associated with Obesogenic Food Consumption and Overweight in 6- to 12-Year-Olds 
Appetite  2012;58(3):1113-1117.
The role of children's personality traits in the consumption of potentially obesogenic foods was investigated in a sample of Norwegian children aged 6–12 years (N = 327, 170 boys, 157 girls). Mothers rated their child's personality on the traits of the Five Factor Model (i.e., Extraversion, Benevolence, Conscientiousness, Neuroticism, and Imagination). Mothers also completed a food frequency questionnaire assessing their child's consumption of sweet drinks, sweet foods, and fruit and vegetables, and reported their child's height and weight. Controlling for age and mothers' education, boys and girls who were less benevolent consumed more sweet drinks, and girls who were less conscientious and more neurotic consumed more sweet drinks. Boys and girls who were more benevolent and imaginative consumed more fruits and vegetables, and boys who were more extraverted, more conscientious, and less neurotic consumed more fruits and vegetables. Controlling for maternal education, boys and girls who were less extraverted, and girls who were less benevolent, less conscientious, and more neurotic were more likely to be overweight or obese. These findings suggest that children's personality traits play an important yet understudied role in their diet. Further investigation of mechanisms that relate child traits to obesogenic eating and overweight would be valuable.
doi:10.1016/j.appet.2012.02.056
PMCID: PMC3340452  PMID: 22425617
Eating; diet; food consumption; weight; obesity; personality; temperament; behavior problems; gender; children
14.  Triple-Antiretroviral Prophylaxis to Prevent Mother-To-Child HIV Transmission through Breastfeeding—The Kisumu Breastfeeding Study, Kenya: A Clinical Trial 
PLoS Medicine  2011;8(3):e1001015.
Timothy Thomas and colleagues report the results of the Kisumu breastfeeding study (Kenya), a single-arm trial that assessed the feasibility and safety of a triple-antiretroviral regimen to suppress maternal HIV load in late pregnancy.
Background
Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT) in resource-limited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretroviral regimen that was designed to maximally suppress viral load in late pregnancy and the first 6 mo of lactation was a safe, well-tolerated, and effective PMTCT intervention.
Methods and Findings
HIV-infected pregnant women took zidovudine, lamivudine, and either nevirapine or nelfinavir from 34–36 weeks' gestation to 6 mo post partum. Infants received single-dose nevirapine at birth. Women were advised to breastfeed exclusively and wean rapidly just before 6 mo. Using Kaplan-Meier methods we estimated HIV-transmission and death rates from delivery to 24 mo. We compared HIV-transmission rates among subgroups defined by maternal risk factors, including baseline CD4 cell count and viral load.
Among 487 live-born, singleton, or first-born infants, cumulative HIV-transmission rates at birth, 6 weeks, and 6, 12, and 24 mo were 2.5%, 4.2%, 5.0%, 5.7%, and 7.0%, respectively. The 24-mo HIV-transmission rates stratified by baseline maternal CD4 cell count <500 and ≥500 cells/mm3 were 8.4% (95% confidence interval [CI] 5.8%–12.0%) and 4.1% (1.8%–8.8%), respectively (p = 0.06); the corresponding rates stratified by baseline maternal viral load <10,000 and ≥10,000 copies/ml were 3.0% (1.1%–7.8%) and 8.7% (6.1%–12.3%), respectively (p = 0.01). None of the 12 maternal and 51 infant deaths (including two second-born infants) were attributed to antiretrovirals. The cumulative HIV-transmission or death rate at 24 mo was 15.7% (95% CI 12.7%–19.4%).
Conclusions
This trial shows that a maternal triple-antiretroviral regimen from late pregnancy through 6 months of breastfeeding for PMTCT is safe and feasible in a resource-limited setting. These findings are consistent with those from other trials using maternal triple-antiretroviral regimens during breastfeeding in comparable settings.
Trial registration
ClinicalTrials.gov NCT00146380
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about half a million children become infected with human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS). Nearly all these newly infected children live in resource-limited countries and most acquire HIV from their mother, so-called mother-to-child transmission (MTCT). Without intervention, 25%–50% of babies born to HIV-positive mothers become infected with HIV during pregnancy, delivery, or breastfeeding. This infection rate can be reduced by treating mother and child with antiretroviral (ARV) drugs. A single dose of nevirapine (a “non-nucleoside reverse transcriptase inhibitor” or NNRTI) given to the mother at the start of labor and to her baby soon after birth nearly halves the risk of MTCT. Further reductions in risk can be achieved by giving mother and baby three ARVs—an NNRTI and two nucleoside reverse transcriptase inhibitors (NRTIs such as zidovudine and lamivudine)—during pregnancy and perinatally (around the time of birth).
Why Was This Study Done?
Breastfeeding is crucial for child survival in poor countries but it is also responsible for up to half of MTCT. Consequently, many researchers are investigating how various ARV regimens given to mothers and/or their infants during the first few months of life as well as during pregnancy and perinatally affect MTCT. In this single-arm trial, the researchers assess the feasibility and safety of using a triple-ARV regimen to suppress the maternal HIV load (amount of virus in the blood) from late pregnancy though 6 months of breastfeeding among HIV-positive women in Kisumu, Kenya, and ask whether this approach achieves a lower HIV transmission rate than other ARV regimens that have been tested in resource-limited settings. In a single-arm trial, all the participants are given the same treatment. By contrast, in a “randomized controlled” trial, half the participants chosen at random are given the treatment under investigation and the rest are given a control treatment. A randomized controlled trial provides a better comparison of treatments than a single-arm trial but is more costly.
What Did the Researchers Do and Find?
In the Kisumu Breastfeeding Study (KiBS), HIV-infected pregnant women took a triple-ARV regimen containing zidovudine and lamivudine and either nevirapine or the protease inhibitor nelfinavir from 34–36 weeks of pregnancy to 6 months after delivery. They were advised to breastfeed their babies (who received single-dose nevirapine at birth), and to wean them rapidly just before 6 months. The researchers then used Kaplan-Meier statistical methods to estimate HIV transmission and death rates among 487 live-born infants from delivery to 24 months. The cumulative HIV transmission rate rose from 2.5% at birth to 7.0% at 24 months. The cumulative HIV transmission or death rate at 24 months was 15.7%; no infant deaths were attributed to ARVs. At 24 months, 3.0% of babies born to mothers with a low viral load were HIV positive compared to 8.7% of babies born to mothers with a high viral load, a statistically significant difference. Similarly, at 24 months, 8.4% of babies born to mothers with low baseline CD4 cell counts (CD4 cells are immune system cells that are killed by HIV; CD4 cell counts indicate the level of HIV-inflicted immune system damage) were HIV positive compared to 4.1% of babies born to mothers with high baseline CD4 cell counts, although this difference did not achieve statistical significance.
What Do These Findings Mean?
Although these findings are limited by the single-arm design, they support the idea that giving breastfeeding women a triple-ARV regimen from late pregnancy to 6 months is a safe, feasible way to reduce MTCT in resource-limited settings. The HIV transmission rates in this study are comparable to those recorded in similar trials in other resource-limited settings and are lower than MTCT rates observed previously in Kisumu in a study in which no ARVs were used. Importantly, the KiBS mothers took most of the ARVs they were prescribed and most stopped breastfeeding by 6 months as advised. The intense follow-up employed in KiBS may be partly responsible for this good adherence to the trial protocol and thus this study's findings may not be generalizable to all resource-limited settings. Nevertheless, they suggest that a simple triple-ARV regimen given to HIV-positive pregnant women regardless of their baseline CD4 cell count can reduce MTCT during pregnancy and breastfeeding in resource-limited setting.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001015.
The accompanying PLoS Medicine Research article by Zeh and colleagues describes the emergence of resistance to ARVs in KiBS
Information on HIV and AIDS is available from the US National Institute of Allergy and Infectious Diseases
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on children, HIV, and AIDS and on preventing mother-to-child transmission of HIV (in English and Spanish)
UNICEF also has information about children and HIV and AIDS (in several languages)
The World Health organization has information on mother-to-child transmission of HIV http://www.who.int/hiv/topics/mtct/en/index.html (in several languages)
doi:10.1371/journal.pmed.1001015
PMCID: PMC3066129  PMID: 21468300
15.  Comparison of anti-retroviral therapy treatment strategies in prevention of mother-to-child transmission in a teaching hospital in Ethiopia 
Pharmacy Practice  2015;13(2):539.
Background:
More than 90% of Human immunodeficiency virus (HIV) infection in children is acquired due to mother-to-child transmission, which is spreading during pregnancy, delivery or breastfeeding.
Objective:
To determine the effectiveness of highly active antiretroviral and short course antiretroviral regimens in prevention of mother-to-child transmission of HIV and associated factors Jimma University Specialized Hospital (JUSH).
Method:
A hospital based retrospective cohort study was conducted on HIV infected pregnant mothers who gave birth and had follow up at anti-retroviral therapy (ART) clinic for at least 6 months during a time period paired with their infants. The primary and secondary outcomes were rate of infant infection by HIV at 6 weeks and 6 months respectively. The Chi-square was used for the comparison of categorical data multivariate logistic regression model was used to identify the determinants of early mother-to-child transmission of HIV at 6 weeks. Cox proportional hazard model was used to analyze factors that affect the 6 month HIV free survival of infants born to HIV infected mothers.
Results:
A total of 180 mother infant pairs were considered for the final analysis, 90(50%) mothers received single dose nevirapine (sdNVP) designated as regimen-3, 67 (37.2%) mothers were on different types of ARV regimens commonly AZT + 3TC + NVP (regimen-1), while the rest 23 (12.8%) mothers were on short course dual regimen AZT + 3TC + sdNVP (regimen-2). Early mother-to-child transmission rate at 6 weeks for regimens 1, 2 and 3 were 5.9% (4/67), 8.6% (2/23), and 15.5% (14/90) respectively. The late cumulative mother-to-child transmission rate of HIV at 6 months regardless of regimen type was 15.5% (28/180). Postnatal transmission at 6 months was 28.5% (8/28) of infected children. Factors that were found to be associated with high risk of early mother-to-child transmission of HIV include duration of ARV regimen shorter than 2 months during pregnancy (OR=4.3, 95%CI =1.38-13.46), base line CD4 less than 350 cells/cubic mm (OR=6.98, 95%CI=0.91-53.76), early infant infection (OR=5.4, 95%CI=2.04-14.4), infants delivered home (OR=13.1, 95%CI=2.69-63.7), infant with birth weight less than 2500 g (OR=6.41, 95%CI=2.21-18.61), and mixed infant feeding (OR=6.7, 95%CI=2.2-20.4). Antiretroviral regimen duration less than 2 months, maternal base line CD4 less than 350 cells/cubic mm and mixed infant feeding were also important risk factors for late infant infection or death.
Conclusion:
The effectiveness of multiple antiretroviral drugs in prevention of early mother-to-child transmission of HIV was found to be more effective than that of single dose nevirapine, although, the difference was not statistically significant. But in late transmission, a significant difference was observed in which infants born to mother who received multiple antiretroviral drugs were less likely to progress to infection or death than infants born to mothers who received single dose nevirapine.
PMCID: PMC4482841  PMID: 26131041
Infectious Disease Transmission; Vertical; Breast Feeding; HIV Infections; Anti-Retroviral Agents; Perinatal Care; Ethiopia
16.  Planned Repeat Cesarean Section at Term and Adverse Childhood Health Outcomes: A Record-Linkage Study 
PLoS Medicine  2016;13(3):e1001973.
Background
Global cesarean section (CS) rates range from 1% to 52%, with a previous CS being the commonest indication. Labour following a previous CS carries risk of scar rupture, with potential for offspring hypoxic brain injury, leading to high rates of repeat elective CS. However, the effect of delivery by CS on long-term outcomes in children is unclear. Increasing evidence suggests that in avoiding exposure to maternal bowel flora during labour or vaginal birth, offspring delivered by CS may be adversely affected in terms of energy uptake from the gut and immune development, increasing obesity and asthma risks, respectively. This study aimed to address the evidence gap on long-term childhood outcomes following repeat CS by comparing adverse childhood health outcomes after (1) planned repeat CS and (2) unscheduled repeat CS with those that follow vaginal birth after CS (VBAC).
Methods and Findings
A data-linkage cohort study was performed. All second-born, term, singleton offspring delivered between 1 January 1993 and 31 December 2007 in Scotland, UK, to women with a history of CS (n = 40,145) were followed up until 31 January 2015. Outcomes assessed included obesity at age 5 y, hospitalisation with asthma, learning disability, cerebral palsy, and death. Cox regression and binary logistic regression were used as appropriate to compare outcomes following planned repeat CS (n = 17,919) and unscheduled repeat CS (n = 8,847) with those following VBAC (n = 13,379).
Risk of hospitalisation with asthma was greater following both unscheduled repeat CS (3.7% versus 3.3%, adjusted hazard ratio [HR] 1.18, 95% CI 1.05–1.33) and planned repeat CS (3.6% versus 3.3%, adjusted HR 1.24, 95% CI 1.09–1.42) compared with VBAC. Learning disability and death were more common following unscheduled repeat CS compared with VBAC (3.7% versus 2.3%, adjusted odds ratio 1.64, 95% CI 1.17–2.29, and 0.5% versus 0.4%, adjusted HR 1.50, 95% CI 1.00–2.25, respectively). Risk of obesity at age 5 y and risk of cerebral palsy were similar between planned repeat CS or unscheduled repeat CS and VBAC. Study limitations include the risk that women undergoing an unscheduled CS had intended to have a planned CS, and lack of data on indication for CS, which may confound the findings.
Conclusions
Birth by repeat CS, whether planned or unscheduled, was associated with an increased risk of hospitalisation with asthma but no difference in risk of obesity at age 5 y. Greater risk of death and learning disability following unscheduled repeat CS compared to VBAC may reflect complications during labour. Further research, including meta-analyses of studies of rarer outcomes (e.g., cerebral palsy), are needed to confirm whether such risks are similar between delivery groups.
Editors' Summary
Background
Women who have had a previous cesarean section (CS) face a slightly elevated risk of negative outcomes during a subsequent vaginal birth. This is because, in rare cases, the abdominal CS scar ruptures during labor, which may cause complications and serious problems, such as oxygen deprivation to the brain of a child. As a result, pregnant women who have had a previous CS and their doctors sometimes make a decision to plan a repeat CS instead of a vaginal birth after cesarean section (VBAC). Besides vaginal birth being “more natural,” some studies have suggested that exposure to the mother’s microbiome (the bacteria and fungi that live in the vagina and gut) in the birth canal might be important for the healthy development of the infant’s own microbiome and its immune system. Consistent with this notion, some studies have reported higher levels of allergies (including eczema and asthma) and overweight or obesity in children born by CS.
Why Was This Study Done?
Scotland keeps detailed records of births and childhood health data, which allow researchers to study possible links between type of birth and subsequent childhood health outcomes. In this study, the researchers focused on singleton births (as opposed to twins, triplets, etc.) to mothers who have had a previous CS. In this group, where the decision about a preferred delivery mode is likely made before labor starts, they examined how childhood health outcomes compared between repeat CS and VBAC.
What Did the Researchers Do and Find?
The researchers studied all second births between 1 January 1993 and 31 December 2007 of singleton children to mothers in Scotland who had previously had a first child born by CS. Using available health records, they categorized these second births into scheduled repeat CS (assumed to be planned), unscheduled repeat CS, and VBAC. They then examined the childrens’ health records until 31 January 2015 and looked for correlations between type of birth and the following outcomes: obesity at age five years, hospitalization with asthma, prescription of a salbutamol inhaler (an asthma medication) at age five, hospitalization with inflammatory bowel disease, type 1 diabetes, learning disability, cerebral palsy, cancer, and death.
Of 40,145 births that took place, 44.6% were scheduled repeat CS, 22.1% were unscheduled repeat CS, and 33.3% were VBAC. The only consistent difference the researchers found between repeat CS (scheduled or unscheduled) and VBAC was a slightly elevated risk for hospitalization with asthma in children born by CS. They felt that this was not clinically significant, especially as there was no difference in the rate of salbutamol inhaler prescription. The risk of obesity at age five was similar between children born by repeat CS (scheduled or unscheduled) and those born by VBAC. Learning disability and death were more common following unscheduled repeat CS, but not scheduled repeat CS, than following VBAC.
What Do These Findings Mean?
Overall, the right decision about a planned birth mode, vaginal or cesarean, depends on the individual case of mother and child. If mothers with a previous CS plan a vaginal birth, they should do so in a hospital that is prepared to perform a CS at short notice in case of scar rupture. The findings here suggest that there are no substantially worse outcomes associated with planned repeat cesarean births. They therefore support a process of planning birth after a previous CS that reflects a woman’s values and preferences. Whether the births analyzed in this study were initially planned to be vaginal or CS is not known. The researchers assumed an intended CS was one that was scheduled ahead of time and performed on the scheduled date. All other CSs were categorized as unplanned and likely represent a mix of emergency CS ahead of a planned CS and emergency CS after complications during a planned vaginal birth. The reasons for the observed higher risk of learning disability and death following unscheduled repeat CS are not clear because the records did not include the indication (i.e., the medical reason) for a CS, but the results are consistent with the known higher risk of an emergency CS to mothers and children.
The risks and benefits of different birth modes, especially in view of exposure to the mother’s microbiome, are active areas of research. The results here disagree with some earlier studies in different settings, but these were unable to adjust for some factors that can affect child health that are taken into account here, such as whether mothers were obese, smoked, or had asthma. The findings of this study are consistent with a study by the same researchers that analyzed all singleton first births from the Scottish health records and found slightly increased asthma rates, but no increased obesity or type 1 diabetes, in young children who had been delivered by CS compared with those who had a vaginal birth.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001973.
The Royal College of Obstetricians and Gynaecologists in the UK has a practice guideline and patient information leaflet on birth after cesarean section
The American Congress of Obstetricians and Gynecologists has a practice bulletin for vaginal birth after previous cesarean delivery, women’s health resources related to vaginal birth after cesarean, and women’s health resources related to cesarean section in general
Wikipedia has a page on delivery after previous cesarean section (note that Wikipedia is an online encyclopedia that anyone can edit)
The Royal Australian and New Zealand College of Obstetricians and Gynaecologists has a statement on birth after previous cesarean section
The Institute of Obstetricians and Gynaecologists of the Royal College of Physicians of Ireland has a clinical practice guideline on delivery after cesarean section
doi:10.1371/journal.pmed.1001973
PMCID: PMC4792387  PMID: 26978456
17.  Predictors of the early introduction of solid foods in infants: results of a cohort study 
BMC Pediatrics  2009;9:60.
Background
The early introduction of solid foods before 4 months of age has been associated with an increased risk of diarrhoea in infancy and a greater risk of wheeze and increased percentage body fat and weight in childhood. The purpose of this study was to identify the level of compliance with national recommendations related to the timing of the introduction of solid foods and to describe the maternal and infant characteristics associated with the timing of the introduction of solids.
Methods
Subjects were 519 participants in the second longitudinal Perth Infant Feeding Study (PIFS II) recruited from two maternity hospitals in Perth, Western Australia in 2002/3. Data collected prior to, or shortly after discharge from hospital, and at 4, 10, 16, 22, 32, 40 and 52 weeks postpartum included timing of the introduction of solid foods and a variety of maternal and infant characteristics associated with the introduction of solid foods. Multivariate logistic regression was used to identify those factors associated with the risk of introducing solid foods early, which for the purposes of this study was defined as being before 17 weeks.
Results
The median age of introduction of solid foods was 17.6 weeks. In total, 44% of infants had received solids before 17 weeks and 93% of infants had received their first solids before 26 weeks of age. The strongest independent predictors of the early introduction of solids were young maternal age, mother smoking prior to pregnancy and not fully breastfeeding at 4 weeks postpartum. In general, mothers introduced solids earlier than recommended because they perceived their baby to either need them or be ready for them.
Conclusion
This study showed a high level of non-compliance among Australian mothers with the infant feeding recommendation related to the timing of solids that was current at the time. In order to improve compliance health professionals need to be aware of those groups least likely to comply with recommendations and their reasons for non-compliance. Infant feeding recommendations need to be evidence-based, uniformly supported by professionals and widely, clearly and consistently articulated if higher rates of compliance are to be achieved in the future.
doi:10.1186/1471-2431-9-60
PMCID: PMC2754451  PMID: 19772610
18.  The Contribution of Infant, Maternal, and Family Conditions to Maternal Feeding Competencies 
SYNOPSIS
Objective
Because little is known about the role of family problem-solving processes in the development of mothers’ competencies in feeding a very low birth-weight (VLBW) infant, we explored the contribution made by the competence in negotiating displayed by a mother and family member as they jointly problem solve infant-care issues. The infant’s neonatal biomedical condition, maternal depressive symptoms, and family poverty status may also contribute to feeding competencies.
Design
A sample of 41 mothers of VLBW infants from 2 longitudinal studies who were observed during feeding at 1 and 8 months infant postterm age, with a family member of their choosing, participated in a dyadic problem-solving exercise. We assessed maternal feeding competencies with the Parent–Child Early Relational Assessment (Clark, 1997) and dyadic negotiating competence using an observational scale from the Iowa Family Interaction Rating Scales (Melby & Conger, 2001). We classified infant condition through medical record audit. Maternal depressive symptoms were assessed with the Center for Epidemiologic Studies-Depression (CES-D) Scale (L. S. Radloff, 1977), and family poverty status was determined through the mother’s report of family income.
Results
Mothers’ feeding competencies, structured into 2 factors, Parental Positive Affective Involvement, Sensitivity, and Responsiveness (PPAISR) and Parental Negative Affect and Behavior (PNAB, scored in the direction of low negativity) were stable from 1 to 8 months, accounting for the entire set of predictor variables. Neonatal biomedical condition had no effect on either PPAISR or PNAB; depressive symptoms were negatively associated with PNAB at 8 months; poverty status negatively predicted both PPAISR and PNAB at 1 and 8 months; and negotiating competence of the mother–family member dyad was positively associated with PNAB at 1 month.
Conclusions
Evidence that family poverty status and dyadic negotiating competence were both associated with maternal feeding competencies supports inclusion of these family-level variables in a model of feeding competencies. A mother’s negotiating competence with another family member who takes a responsible role in infant care may support maternal feeding competencies during a VLBW infant’s early weeks when parenting patterns are forming.
doi:10.1080/15295190903014596
PMCID: PMC3227219  PMID: 22140356
19.  Early maternal relational traumatic experiences and psychopathological symptoms: a longitudinal study on mother-infant and father-infant interactions 
Scientific Reports  2015;5:13984.
Early maternal relational traumas and psychopathological risk can have an impact on mother-infant interactions. Research has suggested the study of fathers and of their psychological profiles as protection or risk factors. The aim of the paper is to assess the quality of parental interactions during feeding in families with mothers with early traumatic experiences. One hundred thirty-six (N = 136) families were recruited in gynecological clinics: Group A included families with mothers who experienced early sexual/physical abuse; Group B was composed of families with mothers who experienced early emotional abuse or neglect; and Group C comprised healthy controls. The subjects participated in a 10-month longitudinal protocol [at the fourth month of pregnancy (T0), 3 months after child birth (T1), and 6 months after child birth (T2)] that included an observation of mother-infant and father-infant interactions during feeding (Scala di Valutazione dell’Interazione Alimentare [SVIA]) and a self-reporting 90-item Symptom Checklist-Revised (SCL-90-R). Maternal higher rates of depression and early traumatic experiences of neglect and emotional abuse predicted more maladaptive scores on the affective state of the dyad SVIA subscale. Paternal anxiety predicted more severe levels of food refusal in the child during feeding.
doi:10.1038/srep13984
PMCID: PMC4564854  PMID: 26354733
20.  Cryptosporidium Prevalence and Risk Factors among Mothers and Infants 0 to 6 Months in Rural and Semi-Rural Northwest Tanzania: A Prospective Cohort Study 
Background
Cryptosporidium epidemiology is poorly understood, but infection is suspected of contributing to childhood malnutrition and diarrhea-related mortality worldwide.
Methods/Findings
A prospective cohort of 108 women and their infants in rural/semi-rural Tanzania were followed from delivery through six months. Cryptosporidium infection was determined in feces using modified Ziehl-Neelsen staining. Breastfeeding/infant feeding practices were queried and anthropometry measured. Maternal Cryptosporidium infection remained high throughout the study (monthly proportion = 44 to 63%). Infection did not differ during lactation or by HIV-serostatus, except that a greater proportion of HIV-positive mothers were infected at Month 1. Infant Cryptosporidium infection remained undetected until Month 2 and uncommon through Month 3 however, by Month 6, 33% of infants were infected. There were no differences in infant infection by HIV-exposure. Overall, exclusive breastfeeding (EBF) was limited, but as the proportion of infants exclusively breastfed declined from 32% at Month 1 to 4% at Month 6, infant infection increased from 0% at Month 1 to 33% at Month 6. Maternal Cryptosporidium infection was associated with increased odds of infant infection (unadjusted OR = 3.18, 95% CI 1.01 to 9.99), while maternal hand washing prior to infant feeding was counterintuitively also associated with increased odds of infant infection (adjusted OR = 5.02, 95% CI = 1.11 to 22.78).
Conclusions
Both mothers and infants living in this setting suffer a high burden of Cryptosporidium infection, and the timing of first infant infection coincides with changes in breastfeeding practices. It is unknown whether this is due to breastfeeding practices reducing pathogen exposure through avoidance of contaminated food/water consumption; and/or breast milk providing important protective immune factors. Without a Cryptosporidium vaccine, and facing considerable diagnostic challenges and ineffective treatment in young infants, minimizing the overall environmental burden (e.g. contaminated water) and particularly, maternal Cryptosporidium infection burden as a means to protect against early infant infection needs prioritization.
Author Summary
Early infancy and childhood Cryptosporidium infection is associated with poor nutritional status, stunted growth, and cognitive deficits, yet minimal research is available regarding the burden and risk factors worldwide. Since there is no vaccine available, and because diagnostic challenges exist and treatment for children younger than one year is ineffective, prevention of early infancy infection through a better understanding of basic epidemiology is critical. This study was designed to investigate symptomatic and clinically silent infection amongst HIV-seropositive and HIV-seronegative mothers and their infants in a longitudinal cohort, and to indentify potential risk factors. Findings indicate that infants are living in a Cryptosporidium environment as demonstrated by the chronically high level of maternal infection throughout the 6-month post-partum period. Despite this, infant infection prevalence remains low until six months of age when it dramatically rises. The increase in infant infection corresponds to a reduction in exclusive breastfeeding. As expected, maternal infection is associated with increased infant infection, but unexpectedly, so is maternal hand washing prior to infant feeding. Since prevention may indeed be the “best medicine” for infants, investigation of beneficial breastfeeding practices, protective correlates in breast milk, and ways to reduce the maternal and environmental Cryptosporidium burden are needed.
doi:10.1371/journal.pntd.0003072
PMCID: PMC4183438  PMID: 25275519
21.  Prenatal and Postnatal Flavor Learning by Human Infants 
Pediatrics  2001;107(6):E88.
Background. Flavors from the mother’s diet during pregnancy are transmitted to amniotic fluid and swallowed by the fetus. Consequently, the types of food eaten by women during pregnancy and, hence, the flavor principles of their culture may be experienced by the infants before their first exposure to solid foods. Some of these same flavors will later be experienced by infants in breast milk, a liquid that, like amniotic fluid, comprises flavors that directly reflect the foods, spices, and beverages eaten by the mother. The present study tested the hypothesis that experience with a flavor in amniotic fluid or breast milk modifies the infants’ acceptance and enjoyment of similarly flavored foods at weaning.
Methods. Pregnant women who planned on breast-feeding their infants were randomly assigned to 1 of 3 groups. The women consumed either 300 mL of carrot juice or water for 4 days per week for 3 consecutive weeks during the last trimester of pregnancy and then again during the first 2 months of lactation. The mothers in 1 group drank carrot juice during pregnancy and water during lactation; mothers in a second group drank water during pregnancy and carrot juice during lactation, whereas those in the control group drank water during both pregnancy and lactation. Approximately 4 weeks after the mothers began complementing their infants’ diet with cereal and before the infants had ever been fed foods or juices containing the flavor of carrots, the infants were videotaped as they fed, in counterbalanced order, cereal prepared with water during 1 test session and cereal prepared with carrot juice during another. Immediately after each session, the mothers rated their infants’ enjoyment of the food on a 9-point scale.
Results. The results demonstrated that the infants who had exposure to the flavor of carrots in either amniotic fluid or breast milk behaved differently in response to that flavor in a food base than did nonexposed control infants. Specifically, previously exposed infants exhibited fewer negative facial expressions while feeding the carrot-flavored cereal compared with the plain cereal, whereas control infants whose mothers drank water during pregnancy and lactation exhibited no such difference. Moreover, those infants who were exposed to carrots prenatally were perceived by their mothers as enjoying the carrot-flavored cereal more compared with the plain cereal. Although these same tendencies were observed for the amount of cereal consumed and the length of the feeds, these findings were not statistically significant.
Conclusions. Prenatal and early postnatal exposure to a flavor enhanced the infants’ enjoyment of that flavor in solid foods during weaning. These very early flavor experiences may provide the foundation for cultural and ethnic differences in cuisine. Pediatrics 2001;107(6). URL: http://www.pediatrics.org/cgi/content/full/107/6/e88; infant nutrition, prenatal, lactation, weaning, flavor, development, preferences.
PMCID: PMC1351272  PMID: 11389286
22.  HIV: mother-to-child transmission 
BMJ Clinical Evidence  2008;2008:0909.
Introduction
Over 2 million children are thought to be living with HIV/AIDS worldwide, of whom over 80% live in sub-Saharan Africa. Without anti-retroviral treatment, the risk of HIV transmission from infected mothers to their children is 15-30% during gestation or labour, and 15-20% during breast feeding. HIV-1 infection accounts for most infections; HIV-2 is rarely transmitted from mother to child. Transmission is more likely in mothers with high viral loads and/or advanced disease, in the presence of other sexually transmitted diseases, and with increased exposure to maternal blood.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of measures to reduce mother to child transmission of HIV? We searched: Medline, Embase, The Cochrane Library and other important databases up to January 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed a GRADE evaluation of the quality of evidence for interventions.
Results
We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiretroviral drugs, different methods of infant feeding, elective caesarean section, immunotherapy, vaginal microbicides, and vitamin supplements.
Key Points
Without active intervention, the risk of mother-to-child transmission (MTCT) of HIV-1 is high, especially in populations where prolonged breast feeding is the norm. Without antiviral treatment, the risk of transmission of HIV from infected mothers to their children is approximately 15-30% during pregnancy and labour, with an additional 10-20% transmission risk attributed to prolonged breast feeding.HIV-2 is rarely transmitted from mother to child.Transmission is more likely in mothers with high viral loads and/or advanced HIV disease.Without antiretroviral treatment (ART), 15-30% of vertically infected infants die within the first year of life.The long-term treatment of children with ART is complicated by multiple concerns regarding the development of resistance, and adverse effects.From a paediatric perspective, successful prevention of MTCT remains the most important focus.
Antiretroviral drugs given to the mother during pregnancy or labour, and/or to the baby immediately after birth, reduce the risk of MTCT of HIV-1.
Reductions in MTCT are possible using simple ART regimens. Longer courses of ART are more effective, but the greatest benefit is derived from treatment during late pregnancy, labour, and early infancy.Suppression of the maternal viral load to undetectable levels (below 50 copies/mL) using highly active antiretroviral therapy (HAART) offers the greatest risk reduction, and is currently the standard of care offered in most resource-rich countries, where MTCT rates have been reduced to 1-2%. Alternative short-course regimens have been tested in resource-limited settings where HAART is not yet widely available. RCTs demonstrate that short courses of antiretroviral drugs have proven efficacy for reducing MTCT. Identifying optimal short-course regimens (drug combination, timing, and cost effectiveness) for various settings remains a focus for ongoing research.
Avoidance of breast feeding prevents postpartum transmission of HIV, but formula feeding requires access to clean water and health education. The risk of breast feeding-related HIV transmission needs to be balanced against the multiple benefits that breast feeding offers. In resource-poor countries, breast feeding is strongly associated with reduced infant morbidity and improved child survival. Modified breastfeeding practices may reduce the risk of HIV transmission while retaining some of its associated benefits.In settings where formula feeding is not feasible (no clean water, insufficient health education, significant cultural barriers) modified breastfeeding practices may offer the best compromise.Early breast feeding with weaning around age 4-6 months may offer an HIV-free survival benefit compared with either formula, mixed feeding, or prolonged breast feeding.Heat- or microbicidal-treated expressed breast milk may offer value in particular settings.
Elective caesarean section at 38 weeks may reduce vertical transmission rates (apart from breast-milk transmission). The potential benefits of this intervention need to be balanced against the increased risk of surgery-associated complications, high cost, and feasibility issues. These reservations are particularly relevant in resource-limited settings.
Immunotherapy with HIV hyperimmune globulin or immunoglobulin without HIV antibody does not reduce HIV-1 MTCT risk.
Vaginal microbiocides have not been demonstrated to reduce HIV-1 MTCT risk.
There is no evidence that vitamin A or multivitamin supplementation reduces the risk of HIV-1 MTCT or infant mortality.
PMCID: PMC2907958  PMID: 19450331
23.  Predictors for early introduction of solid food among Danish mothers and infants: an observational study 
BMC Pediatrics  2014;14:243.
Background
Early introduction of complementary feeding may interfere with breastfeeding and the infant’s self-controlled appetite resulting in increased growth. The aim of the present study was to investigate predictors for early introduction of solid food.
Methods
In an observational study Danish mothers filled in a self-administered questionnaire approximately six months after birth. The questionnaire included questions about factors related to the infant, the mother, attachment and feeding known to influence time for introduction of solid food. The study population consisted of 4503 infants. Data were analysed using ordered logistic regression models. Outcome variable was time for introduction to solid food.
Results
Almost all of the included infants 4386 (97%) initiated breastfeeding. At weeks 16, 17–25, 25+, 330 infants (7%); 2923 (65%); and 1250 (28%), respectively had been introduced to solid food. Full breastfeeding at five weeks was the most influential predictor for later introduction of solid food (OR = 2.52 CI: 1.93-3.28). Among infant factors male gender, increased gestational age at birth, and higher birth weight were found to be statistically significant predictors. Among maternal factors, lower maternal age, higher BMI, and being primipara were significant predictors, and among attachment factors mother’s reported perception of the infant as being temperamental, and not recognising early infant cues of hunger were significant predictors for earlier introduction of solid food. Supplementary analyses of interactions between the predictors showed that the association of maternal perceived infant temperament on early introduction was restricted to primiparae, that the mother’s pre-pregnancy BMI had no impact if the infant was fully breastfed at week five, and that birth weight was only associated if the mother had reported early uncertainty in recognising infant’s cues of hunger.
Conclusions
Breastfeeding was the single most powerful indicator for preventing early introduction to solid food. Modifiable predictors pointed to the importance of supporting breastfeeding and educating primipara and mothers with low birth weight infants to be able to read and respond to their infants’ cues to prevent early introduction to solid food.
doi:10.1186/1471-2431-14-243
PMCID: PMC4263048  PMID: 25270266
Infant feeding practices; Breast-feeding; Introduction of complementary feeding; Solid food; Infant temperament; Risk factors
24.  Common risk factor approach to address socioeconomic inequality in the oral health of preschool children – a prospective cohort study 
BMC Public Health  2014;14:429.
Background
Dental caries remains the most prevalent chronic condition in children and a major contributor to poor general health. There is ample evidence of a skewed distribution of oral health, with a small proportion of children in the population bearing the majority of the burden of the disease. This minority group is comprised disproportionately of socioeconomically disadvantaged children. An in-depth longitudinal study is needed to better understand the determinants of child oral health, in order to support effective evidence-based policies and interventions in improving child oral health. The aim of the Study of Mothers’ and Infants’ Life Events Affecting Oral Health (SMILE) project is to identify and evaluate the relative importance and timing of critical factors that shape the oral health of young children and then to seek to evaluate those factors in their inter-relationship with socioeconomic influences.
Methods/Design
This investigation will apply an observational prospective study design to a cohort of socioeconomically-diverse South Australian newborns and their mothers, intensively following these dyads as the children grow to toddler age. Mothers of newborn children will be invited to participate in the study in the early post-partum period. At enrolment, data will be collected on parental socioeconomic status, mothers’ general and dental health conditions, details of the pregnancy, infant feeding practice and parental health behaviours and practices. Data on diet and feeding practices, oral health behaviours and practices, and dental visiting patterns will be collected at 3, 6, 12 and 24 months of age. When children turn 24-30 months, the children and their mothers/primary care givers will be invited to an oral examination to record oral health status. Anthropometric assessment will also be conducted.
Discussion
This prospective cohort study will examine a wide range of determinants influencing child oral health and related general conditions such as overweight. It will lead to the evaluation of the inter-relationship among main influences and their relative effect on child oral health. The study findings will provide high level evidence of pathways through which socio-environmental factors impact child oral health. It will also provide an opportunity to examine the relationship between oral health and childhood overweight.
doi:10.1186/1471-2458-14-429
PMCID: PMC4039048  PMID: 24885129
Children; Early childhood caries; Socioeconomic inequality; Prospective cohort study
25.  Associations between gestational anthropometry, maternal HIV, and fetal and early infancy growth in a prospective rural/semi-rural Tanzanian cohort, 2012-13 
Background
Healthcare access and resources differ considerably between urban and rural settings making cross-setting generalizations difficult. In resource-restricted rural/semi-rural environments, identification of feasible screening tools is a priority. The objective of this study was to evaluate gestational anthropometry in relation to birth and infant growth in a rural/semi-rural Tanzanian prospective cohort of mothers and their infants.
Methods
Mothers (n = 114: 44 HIV-positive) attending antenatal clinic visits were recruited in their second or third trimester between March and November, 2012, and followed with their infants through 6-months post-partum. Demographic, clinical, and infant feeding data were obtained using questionnaires administered by a Swahili-speaking research nurse on demographic, socioeconomic, clinical, and infant feeding practices. Second or third trimester anthropometry (mid-upper arm circumference [MUAC], triceps skinfold thickness, weight, height), pregnancy outcomes, birth (weight, length, head circumference) and infant anthropometry (weight-for-age z-score [WAZ], length-for-age z-score [LAZ]) were obtained. Linear regression and mixed effect modeling were used to evaluate gestational factors in relation to pregnancy and infant outcomes.
Results and discussion
Gestational MUAC and maternal HIV status (HIV-positive mothers = 39 %) were associated with infant WAZ and LAZ from birth to 6-months in multivariate models, even after adjustment for infant feeding practices. The lowest gestational MUAC tertile was associated with lower WAZ throughout early infancy, as well as lower LAZ at 3 and 6-months. In linear mixed effects models through 6-months, each 1 cm increase in gestational MUAC was associated with a 0.11 increase in both WAZ (P < 0.001) and LAZ (P = 0.001). Infant HIV-exposure was negatively associated with WAZ (β = -0.65, P < 0.001) and LAZ (β = -0.49, P < 0.012) from birth to 6-months.
Conclusions
Lower gestational MUAC, evaluated using only a tape measure and minimal training that is feasible in non-urban clinic and community settings, was associated with lower infant anthropometric measurements. In this rural and semi-rural setting, HIV-exposure was associated with poorer anthropometry through 6-months despite maternal antiretroviral access. Routine assessment of MUAC has the potential to identify at-risk women in need of additional health interventions designed to optimize pregnancy outcomes and infant growth. Further research is needed to establish gestational MUAC reference ranges and to define interventions that successfully improve MUAC during pregnancy.
doi:10.1186/s12884-015-0718-6
PMCID: PMC4625530  PMID: 26515916
Africa; HIV/AIDS; HIV-exposed; MUAC; Maternal; Nutrition; Point-of-care; Stunting; Triceps skinfold; Tanzania

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