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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
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A gene that reinforces maternal attachment?

A particular variation in the serotonin gene SLC6A4, makes some children four times more likely to strongly attach to their mothers. The observation was made following a mentoring program for their mothers to improve mom's own attachment behaviors.

The study was supported by the Government of Canada through Grand Challenges Canada Saving Brains program. It sheds new light on why some children benefit more than others from social interventions. It also raises complex questions about psychosocial intervention programs. The work was published February 28 in PLoS Medicine

The study was led by Professor Mark Tomlinson of Stellenbosch University, a public research university situated in Stellenbosch, South Africa. It followed-up on an intervention conducted between 1999 and 2003, in which expectant mothers were mentored to improve attachment with their children. The goal was to improve a child's psychological security and future wellbeing. In the original study, a control group of about the same size of expectant mothers were not mentored in behaviors.

The original study concluded that the intervention had a small-to-moderate effect on mother-child attachment. Evaluations were conducted once a child reached 18 months of age.

The follow-up study, conducted thirteen years after the first intervention, re-examined the original attachment results and found something new: The intervention had in fact worked well for toddlers with a particular genetic characteristic.

Collaborating with colleagues from the University of Reading, Reading, Berkshire, United Kingdom and the University College London, England and Western University, London, Ontario, Canada — the new study re-enrolled and conducted genetic tests on 279 of the original 449 children. Of those original 279 children, 220 produced both genetic and attachment data which enabled investigators to re-test whether the original attachment outcomes were influenced by a child's genetics.

Researchers factored in whether a child had the short or long form of gene SLC6A4 — the serotonin transporter gene, involved in nerve signals received in the brain. Other studies have linked SLC6A4 to anxiety as well as depression as reflected in the amount of serotonin produced. Serotonin is popularly thought to contribute to feelings of well-being and happiness. However, it has a more complicated or flexible purpose.

Although elevated or happy emotional findings have been hinted at with serotonin before, this study is one of the best demonstrations that SLC6A4, or the S gene, is neither a good gene nor a bad gene — but a flexible gene. It appears to be able to make an individual more sensitive to his or her environment, in this particular study, happy and loving when influenced positively in childhood. If the childhood environment is safe and nurturing, it appears this safety is replicated in the adult. Facing later disappointment, or depressions, the happy child does not bring the adult to a break down.

On the other hand, if the childhood environment is harsh, a propensity toward high-risk behavior is fostered. Under those circumstances the S gene is associated with earlier sexual activity and more substance abuse.

Children with the short form of the S gene whose pregnant mothers were mentored, were almost four times more likely to be emotionally attached to mom by 18 months old — 84 % being securely attached. But, in children carrying the short form of the S gene whose pregnant mothers were not mentored, only 58 % securely attached.

Also, children with the long form of the S gene were apparently unaffected by their mother's training or lack of training. In either case, their secure attachment to their mothers was almost identical at 70 and 71% by 18 months old.

So, the research out of South Africa suggests a child's genetic make-up can play a large, hidden role in the success of efforts to maximize his or her development.

Subject to further validation, says Professor Tomlinson, the insight has "important implications for scientists designing and evaluating interventions to benefit as many people as possible in South Africa and worldwide. Without taking genetics into account, it is possible that other studies have under-estimated the impact of their interventions, as we originally did."

Researchers caution that this study involved a relatively small sample and only measured one gene and one outcome — attachment.

Says Dr. Peter A. Singer, Chief Executive Officer of Grand Challenges Canada: "This is a startling finding that changes the way I think about child development. Why is it important? Because child development is the ladder of social mobility used to climb out of the hole of inequity by millions of children around the world."

Clear recognition of the damaging effects of poverty on early childhood development has fueled an interest in interventions aimed at mitigating these harmful consequences. Psychosocial interventions aimed at alleviating the negative impacts of poverty on children are frequently shown to be of benefit, but effect sizes are typically small to moderate. However, averaging outcomes over an entire sample, as is typically done, could underestimate efficacy because weaker effects on less susceptible individuals would dilute estimation of effects on those more disposed to respond. This study investigates whether a genetic polymorphism of the serotonin transporter gene moderates susceptibility to a psychosocial intervention.

Methods and findings
We reanalyzed data from a randomized controlled trial of a home-visiting program delivered by community health workers in a black, isiXhosa-speaking population in Khayelitsha, South Africa. The intervention, designed to enhance maternal-infant attachment, began in the third trimester and continued until 6 mo postpartum. Implemented between April 1999 and February 2003, the intervention comprised 16 home visits delivered to 220 mother–infant dyads by specially trained community health workers. A control group of 229 mother–infant dyads did not receive the intervention. Security of maternal-infant attachment was the main outcome measured at infant age 18 mo. Compared to controls, infants in the intervention group were significantly more likely to be securely attached to their primary caregiver (odds ratio [OR] = 1.7, p = 0.029, 95% CI [1.06, 2.76], d = 0.29). After the trial, 162 intervention and 172 control group children were reenrolled in a follow-up study at 13 y of age (December 2012–June 2014). At this time, DNA collected from 279 children (134 intervention and 145 control) was genotyped for a common serotonin transporter polymorphism. There were both genetic data and attachment security data for 220 children (110 intervention and 110 control), of whom 40% (44 intervention and 45 control) carried at least one short allele of the serotonin transporter gene. For these 220 individuals, carrying at least one short allele of the serotonin transporter gene was associated with a 26% higher rate of attachment security relative to controls (OR = 3.86, p = 0.008, 95% CI [1.42, 10.51], d = 0.75), whereas there was a negligible (1%) difference in security between intervention and control group individuals carrying only the long allele (OR = 0.95, p = 0.89, 95% CI [0.45, 2.01], d = 0.03). Expressed in terms of absolute risk, for those with the short allele, the probability of secure attachment being observed in the intervention group was 84% (95% CI [73%, 95%]), compared to 58% (95% CI [43%, 72%]) in the control group. For those with two copies of the long allele, 70% (95% CI [59%, 81%]) were secure in the intervention group, compared to 71% (95% CI [60%, 82%]) of infants in the control group. Controlling for sex, maternal genotype, and indices of socioeconomic adversity (housing, employment, education, electricity, water) did not change these results. A limitation of this study is that we were only able to reenroll 49% of the original sample randomized to the intervention and control conditions. Attribution of the primary outcome to causal effects of intervention in the present subsample should therefore be treated with caution.

When infant genotype for serotonin transporter polymorphism was taken into account, the effect size of a maternal-infant attachment intervention targeting impoverished pregnant women increased more than 2.5-fold when only short allele carriers were considered (from d = 0.29 for all individuals irrespective of genotype to d = 0.75) and decreased 10-fold when only those carrying two copies of the long allele were considered (from d = 0.29 for all individuals to d = 0.03). Genetic differential susceptibility means that averaging across all participants is a misleading index of efficacy. The study raises questions about how policy-makers deal with the challenge of balancing equity (equal treatment for all) and efficacy (treating only those whose genes render them likely to benefit) when implementing psychosocial interventions.

About Grand Challenges Canada
Grand Challenges Canada is dedicated to supporting Bold Ideas with Big Impact® in global health. We are funded by the Government of Canada and we support innovators in low- and middle-income countries and Canada. The bold ideas we support integrate science and technology, social and business innovation - we call this Integrated Innovation®. Grand Challenges Canada focuses on innovator-defined challenges through its Stars in Global Health program and on targeted challenges in its Saving Lives at Birth, Saving Brains and Global Mental Health programs. Grand Challenges Canada works closely with Canada's International Development Research Centre (IDRC), the Canadian Institutes of Health Research (CIHR) and Global Affairs Canada to catalyze scale, sustainability and impact. We have a determined focus on results, and on saving and improving lives. http://www.grandchallenges.ca

About Saving Brains
Saving Brains is a partnership of Grand Challenges Canada, Aga Khan Foundation Canada, the Bernard van Leer Foundation, the Bill & Melinda Gates Foundation, The ELMA Foundation, Grand Challenges Ethiopia, the Maria Cecilia Souto Vidigal Foundation, the Palix Foundation, UBS Optimus Foundation and World Vision Canada. It seeks and supports bold ideas for products, services and implementation models that protect and nurture early brain development relevant to poor, marginalized populations in low- or middle-income countries. http://www.savingbrainsinnovation.net


Mar 6, 2017   Fetal Timeline   Maternal Timeline   News   News Archive   

A South African child is evaluated as part of a Stellenbosch University study.
Image Credit: Stellenbosch University



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