Multiple Micronutrient Supplementation During Pregnancy and Birth Outcomes in Low-Income Countries

I thank John Ovretveit (Karolinksa Institutet, Sweden) for bringing this important Lancet article to my attention.[1]

The study is a meta-analysis of individual patient data from 17 RCTs in low- and middle-income countries. The use of individual patient data enables multiple sub-group analyses to be carried out.

This paper confirms some things we already know. For example, iron reduces pre-term delivery and low birth weight. The effect is much greater in anaemic woman in both low- and high-income countries. Iron and folic acid combined have a more powerful effect on reducing these outcomes than either iron or folic acid alone.

This paper shows that including at least one further micronutrient has additional benefit. It also shows that multiple micronutrients reduce neonatal mortality, but only among girls. There is no solid biological explanation for this observation. Consistent with the underlying hypothesis, starting micronutrients early in pregnancy, and high adherence were associated with larger effect sizes. Importantly, no harms were demonstrated for micronutrients.

I recently summarised evidence regarding micronutrients for adults in high-income countries.[2] Here there was no evidence of benefit and evidence of harm with high doses of mineral supplementation. I would still be cautious about liberal use of mineral supplements in pregnancy, with the exception of iron.

— Richard Lilford, CLAHRC WM Director

References:

1. Smith ER, Shankar AH, Wu LS, et al. Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: a meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries. Lancet Glob Health. 2017; 5(11):e1090-100.
2. Lilford RJ. Stop Taking Those Supplements: Just Stop. NIHR CLAHRC West Midlands News Blog. 7 June 2019.

Food Allergies and Childbirth

In a previous News Blog we looked at the practice of swabbing babies delivered via Caesarean section with vaginal fluid in an attempt to reduce the incidence of allergies in the child.[1] Another study has now been reported that could potentially strengthen this argument.[2] This was a nationwide cohort study conducted in Sweden that looked at over 1 million children, their route of delivery and the incidence of food allergies. Overall 2.5% of children were diagnosed with a food allergy, and this was positively associated with those who were delivered via C-section (hazard ratio 1.21, 95% CI 1.18-1.25) – both elective and emergency. Analysis of the data suggests that an extra 5 in 1,000 children delivered via C-section would develop a food allergy (compared to the reference group).

Interestingly there was also a negative association with those who were born prematurely (earlier than 32 weeks) (HR 0.74, 95% CI 0.56-0.98). The authors suggest this may be due to the postnatal care preterm infants receive, or is due to an immature gastrointestinal tract.

— Peter Chilton, Research Fellow

References:

1. Lilford RJ. Exposure of the Baby to a Rich Mixture of Coliform Organisms from the Birth Canal. NIHR CLAHRC West Midlands News Blog. 22 April 2016.
2. Mitselou N, Hallberg J, Stephansson O, Almqvist C, Melén E, Ludvigsson JF. Cesarean delivery, preterm birth, and risk of food allergy: Nationwide Swedish cohort study of more than 1 million children. J Allerg Clin Immunol. 2018.

Hidden Disadvantage to Caesarean Section

Some modern health care may end up changing the genetics of the human race. For example, the CLAHRC WM Director established a genetic basis for male infertility,[1] and sure enough, children born following injection of sperm into the mother’s egg have an increased risk of infertility.[2] What about Caesarean section? Childbirth is a struggle because, compared to all other animals (primates included), the baby’s head is big relative to the size of the mother’s pelvis. Evolution allows this to continue under an equilibrium where the distribution of pelvic sizes is maintained at a level where the beneficial effects of big brain/head balances the risk of catastrophic birth from a pelvis below the threshold where risk rises rapidly. Caesarean section skews natural selection and pelvic sizes according to this elegant mathematical model.[3] But are pelvic sizes indeed becoming smaller?

— Richard Lilford, CLAHRC WM Director

References:

1. Lilford R, Jones AM, Bishop DT, Thornton J, Mueller R. Case-control study of whether subfertility in men is familial. BMJ. 1994; 309: 570.
2. Belva F, Bonduelle M, Roelants M, et al. Semen quality of young adult ICSI offspring: the first results. Hum Reprod. 2016; 31(12): 2811-20.
3. Mitteroecker P, Huttegger SM, Fischer B, Pavlicev M. Cliff-edge model of obstetric selection in humans. P Natl Acad Sci USA. 2016.

Support for Pregnant Teenagers

News blog readers are (anxiously) awaiting publication of the important CLAHRC study of the effects providing additional support to mothers at high social risk. In the meantime, we must content ourselves with a study of additional support in teenage pregnancy.[1] The support was intensive and, as in the CLAHRC study, it started before birth and continued postnatally. Study numbers were similar to the CLAHRC study at over 1,600 participants. The results were null for the pre-defined ‘primary’ outcomes of birth weight, childhood admissions and subsequent pregnancy. But are these the sorts of end-point that one would expect to change? Programme theory would surely suggest that a social intervention would change social outcomes?! Yet, these were relegated to ‘secondary outcome’ status. The results of the CLAHRC study are becoming more tantalising with every passing week!

— Richard Lilford, CLAHRC WM Director

References:

1. Robling M, Bekkers M-J, Bell K, et al. Effectiveness of a nurse-led intensive home-visitation programme for first-time teenage mothers (Building Blocks): a pragmatic randomised controlled trial. Lancet. 2015. [ePub].

Using Real-Time Simulation to Improve the Dialogue when Discussing Women’s Options for Place of Birth

CLAHRC WM Theme 1, Maternity and Child Health, has been involved in carrying out some simulation training with midwives as part of their ‘place of birth’ study. This study has explored midwives’ views of their discussions with women about their options for where to give birth and followed on from the 2011 Birthplace study,[1] which found that for low risk, multiparous women, there was no significant difference in composite perinatal outcomes between women who gave birth in obstetric units, in maternity led units, or at home. Despite this, many women are not offered the full range of birth place options by their midwife and are often unaware that they have a choice about where they can choose to give birth, instead viewing hospital as the ‘default’ option.[2] The ‘place of birth’ study aimed to help promote choice of place of birth in midwives’ discussions with women. This involved a co-production approach, with midwives being involved in the study process and design. Findings from the literature, focus groups with midwives and a preliminary midwifery workshop resulted in identification of the need for a pragmatic, standardised ‘place of birth’ dialogue, that midwives could use as a tool for use in their discussions with women about where to give birth. A provisional draft of this dialogue was put together by midwives working at BWNFT (with input and guidance from the CLAHRC team) and covered aspects relating to the safety and practicalities of giving birth at home, in the Birth Centre and in Delivery Suite. It aimed to use appropriate language and openers so that women would consider all three of the birth place options available to them.

We decided to use role players in a second midwifery and PPI workshop to simulate the interactions between a midwife and a woman when using the dialogue. This was to explore how well the dialogue worked in ‘real’ practice and whether it sounded right or needed amending. At the workshop, two female role players acted out the dialogue (one playing a midwife and one a pregnant woman) and workshop attendees had the opportunity to modify the dialogue based on what sounded and felt right and what didn’t, until a finalised dialogue for multiparous women was agreed on. This process was repeated again, but for nulliparous women, resulting in the formation of two slightly different dialogues, due to differences in safety and risk meaning that slightly different information needed to be conveyed.

The role playing and subsequent discussions were audio recorded to allow any changes to the dialogue which were agreed on to be saved and transcribed. This ensured that a precise final dialogue could be written up by the CLAHRC team, which accurately detailed what was agreed on by the midwives and PPI during the workshop session. This finalised dialogue is intended as a prompt and a supportive tool to convey the sort of information midwives should be giving to women when talking to them about their place of birth options, rather than a script which midwives have to rigidly stick to. However, the final dialogue should convey a true reflection of what works in practice, to provide a useful resource to midwives when thinking about how to approach these discussions.

The role playing was very well received by the midwives and PPI representatives and encouraged interaction, discussion and debate as to the best way to approach place of birth discussions with women. Having the role players present at the workshop meant that any suggested changes to the dialogue could be incorporated and re-enacted by the role players, until a version of the dialogue emerged that had been developed and refined by the midwives who will be using the dialogue in their everyday practice.

The CLAHRC team are continuing to work with midwives at BWNFT to think about the best ways of successfully implementing the place of birth dialogue into midwives everyday practice. We have utilised the COM-B framework [3] to identify a variety of behaviour change techniques that might be useful mechanisms to help embed the dialogue in the short and longer term. We are currently finalising a protocol to support the implementation of the place of birth dialogue in clinical practice and to evaluate how successful it has been in changing the way that midwives talk to women about their options for where to give birth.

— Catherine Shneerson, Research Fellow, CLAHRC WM Theme 1

References

1. Birthplace in England Collaborative Group. Perinatal and maternal outcomes by planned place of birth for healthy women with low risk pregnancies: the Birthplace in England national prospective cohort study. BMJ 2011; 343: d7400
2. Coxon K, Sandall J, Fulop N J. To what extent are women free to choose where to give birth? How discourses of risk, blame and responsibility influence birth place decisions. Health, Risk & Society. 2014; 16(1): 52-67.
3. Michie S, van Stralen M, West R. The behaviour change wheel: a new method for characterising and designing behaviour change interventions. Implement Sci. 2011; 6: 42.

Birth Interval and Birth Weight

Short gaps (less than two years) between pregnancies have been shown again and again to be associated with poorer birth outcomes (particularly smaller babies) than medium length gaps (3-5 years), even after controlling for identifiable confounders such as maternal age. This result was replicated by Ball et al.,[1] but they made a further analysis in which mothers who had had at least three children acted as their own controls. The association between short birth interval and low birth weight disappears. So it would appear that both events – birth interval and birth weight – are linked by underlying biological factors. The lesson – whenever possible look for differences within person, before comparing the differences across people, and remain very sceptical about cause and effect associations based on cross-sectional risk-adjustment alone.

— Richard Lilford, CLAHRC WM Director

Reference:

1. Ball SJ, Pereira G, Jacoby P, de Klerk N, Stanley FJ. Re-evaluation of link between interpregnancy interval and adverse birth outcomes: retrospective cohort study matching two intervals per mother. BMJ. 2014; 349: g4333.