Tag Archives: Pregnancy

Computer Interpretation of Foetal Heart Rates Does Not Help Distinguishing Babies That Need a Caesarean from Those That Do Not

In an earlier life I was involved in obtaining treatment costs for a pilot trial of computerised foetal heart monitoring versus standard foetal heart monitoring (CTG). The full trial, funded by NIHR, has now been published in the Lancet,[1] featuring Sara Kenyon from our CLAHRC WM theme 1. With over 46,000 participants the trial found no difference in a composite measure of foetal outcome or intervention rates. Perinatal mortality was only 3 per 10,000 women across both arms and the incidence of hypoxic encephalopathy was less than 1 per 1,000. Of course, the possibility of an educational effect from the computer decision support (‘contamination’) may have reduced the observed effect, but this could only be tested by a cluster trial. However, such a design would create its own set of problems, such as loss of precision and bias through interaction between method used and baseline risk across interventions and control sites. Also, the control group was not care as usual, but the visual display IT system shorn of its decision support (artificial intelligence) module.[2] Some support for the idea that control condition affected care in a positive direction, making any marginal effect of decision support hard to detect, comes from the low event rate across both study arms. Meanwhile, the lower than expected baseline event rates mean that any improvement in outcome will be hard to detect in future studies. So here is another topic that, like vitamin D given routinely to elderly people,[3] now sits below the “horizon of science” – the combination of low event rates and low plausible effect sizes mean that we can move on from this subject – at least in a high-income context. If you want to use the computerised method, and its costs are immaterial, then there is no reason not to; economics aside there appear to be no trade-offs here, since both benefits and harms were null.

— Richard Lilford, CLAHRC WM Director

References:

  1. The INFANT Collaborative Group. Computerised interpretation of fetal heart rate during labour (INFANT): a randomised controlled trial. Lancet. 2017.
  2. Keith R. The INFANT study – a flawed design foreseen. Lancet. 2017.
  3. Lilford RJ. Effects of Vitamin D Supplements. NIHR CLAHRC West Midlands News Blog. 24 March 2017.

Pregnancy Before Age 16 – Dropping Quite Rapidly From a Peak in 1997

Tracking four databases, a recent study finds sharply falling ‘teenage pregnancy’ rates in England, starting in 1997 and accelerating in 2007.[1] Rates have fallen fastest in the most deprived areas, albeit from a very high base. The reduction has been much larger in England than in other European countries where the decline is also observed. It is difficult to know exactly why, but proximal causes (increasing availability of long-acting contraception) and distal causes (gradually improving educational standards in England) are both correlated in this study with lower teenage pregnancy. I think we should go even further in removing barriers to use of contraception in young people – for instance it should be available without prescription, or if prescription is required it should be available on site, given evidence cited in a previous News Blog.[2]
— Richard Lilford, CLAHRC WM Director

Reference:

  1. Wellings K, Palmer MJ, Geary RS, et al. Changes in Conceptions in Women Younger Than 18 Years and the Circumstances of Young Mothers in England in 2000-12: an Observational Study. Lancet. 2016; 388: 586-95.
  2. Lilford RJ. Contraception – a Huge Cause of Controversy Around the World. NIHR CLAHRC West Midlands News Blog. August 8, 2014.

Okay Then, There is a Fourth Period of Whole-Scale Synaptic Pruning in the Grey Matter of the Brain

This News Blog has frequently discussed synaptic pruning [1] [2] – a process that occurs in the foetus at mid-gestation, children at around the age of two, and in late adolescence. Abnormalities in neural synaptic pruning are associated with diseases, such as schizophrenia and autism.[3] It turns out that there is another period of synaptic pruning – during pregnancy. Functional MRI shows that many areas of grey matter shrink in pregnancy. Greater pruning is associated with higher scores on standard questionnaires measuring a mother’s attachment to her baby.[4] More brain does not necessarily mean better brain.

— Richard Lilford, CLAHRC WM Director

References:

  1. Lilford RJ. Psychiatry Comes of Age. NIHR CLAHRC West Midlands News Blog. 11 March 2016.
  2. Lilford RJ. A Fascinating Account of the Opening Up of an Area of Scientific Enquiry. NIHR CLAHRC West Midlands News Blog. 11 November 2016.
  3. van Spronsen M, Hoogenraad CC. Synapse Pathology in Psychiatric and Neurologic Disease. Curr Neurol Neurosci Rep. 2010; 10(3): 207-14.
  4. Hoekzema E, Barba-Müller E, Pozzobon C, et al. Pregnancy leads to long-lasting changes in human brain structure. Nature Neurosci. 2016.

If You Want to Reduce Partner Violence or Teenage Pregnancy, Then Teach Algebra and History?

There is little doubt that highly educated men are less likely than poorly educated men to perpetrate violence against their partners,[1] and that highly educated women are less likely than poorly educated women to get pregnant in their teens.[2] But what is going on here – which way does causality run? Certainly, an educated man is likely to earn more than one less educated. More money means less stress, and since stress is a harbinger of partner violence, it is plausible that education leads to less violence through this mediating (intervening) variable. Alternatively, the kind of person who acquires education may be the sort of person who is less innately pre-disposed to violence than a person who does not acquire education. A person who seeks out education may have greater mental resources, such that a wider range of responses are available to him – and hence he is less likely to lash out. But could it be that education per se increases moral rectitude, even when the education is not targeted at moral behaviour? One can devise a theory for such an effect. Algebra, history and other ‘academic’ subjects exercise the capacity for abstract thought. Could the capacity spill over from the topic of instruction to influence behaviour more generally? Compassion, for example, is abstract – it requires the ability to imagine what another person is feeling. Teaching abstract academic subjects may spill over in to heightened sensitivity to the suffering of others. This hypothesis could be tested neurophysiologically – highly educated persons, on average, may manifest greater specific responses on functional neuro-imaging than those of similar IQ, but lower educational attainment, when confronted with a compassion-arousing event. The brain, after all, is a learning machine that is permanently altered by education. This might explain why sex education has a rather small effect on teenage pregnancy, but being educated is associated with a large effect. It is sometimes said that education refers to what is left when all the facts have been forgotten, or to quote BF Skinner more accurately, “Education is what survives when what has been learnt has been forgotten”?

— Richard Lilford, CLAHRC WM Director

References:

  1. Abramsky T, Watts CH, Garcia-Moreno C, et al. What factors are associated with recent intimate partner violence? findings from the WHO multi-country study on women’s health and domestic violence. BMC Public Health. 2011; 11: 109.
  2. Girma S & Paton D. Is education the best contraception: The case of teenage pregnancy in England? Soc Sci Med. 2015; 131: 1-9.

Update on Zika for News Blog Readers

A recent review of epidemiological evidence from the Center for Disease Control (CDC) in Atlanta confirms the association of Zika arbovirus infections during pregnancy with microcephaly in the infant, with a risk of about one in 100.[1] It is probable that the risk of neurological effects less serious than microcephaly is also increased. A recent BMJ paper [2] analyses a cohort of microcephalic children born of mothers with Zika virus infection in pregnancy. They did not just measure the size of the head relative to length and weight. All babies underwent CT scan, MRI, or both. They all manifested strikingly similar features on neuro-imaging, and these features are largely distinct from the other known causes of microcephaly, including those associated with infections with other viruses, such as cytomegalovirus. The famous philosopher of science William Whewell, argued that if information of different types all corroborate the same theory, then that is powerful support in its favour.[3] The CLAHRC WM Director thinks a causal role for the virus is pretty much settled – we may assume that the Zika virus is indeed a cause of severe (and perhaps less severe) neurological damage in the foetus.

— Richard Lilford, CLAHRC WM Director

References:

  1. Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika Virus and Birth Defects — Reviewing the Evidence for Causality. N Engl J Med. 2016; 374: 1981-7.
  2. Aragao MFV, van der Linden V, Brainer-Lima AM, et al. Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study. BMJ. 2016; 353: i1901.
  3. Whewell W & Butts RE. William Whewell’s Theory of Scientific Method. Pittsburgh: University of Pittsburgh Press. 1968.

Cluster Trial of Home Visits for Newborn Children in Sub-Saharan Africa

Forty percent of childhood deaths in low- and middle-income countries (LMICs) take place within the first month after birth. Trials conducted in Asia have shown that an intervention whereby home-visits are made over this crucial period of life is effective. Would it work in Africa? To find out, Betty Kirkwood and colleagues randomised 197 clusters in Ghana to intervention and control.[1] Mothers in the intervention clusters were to receive two home visits in pregnancy and three in the first week after birth. Coverage was good and the proportion of mothers who adopted health promoting behaviours increased. These behaviours included use of anti-mosquito bed-nets, timely transfer to a facility when appropriate, breastfeeding, ‘kangaroo’ care, delayed bathing of the baby, and hand-washing. Reductions in neonatal mortality observed in this trial alone were not significant, but a significant 12% reduction in mortality was estimated when the data were combined with those from the Asian trials in a meta-analysis. The CLAHRC WM Director could not find out whether the study was rural or urban. Trials of women’s groups [2] provide positive results in rural areas but not slums. It would be interesting to examine the effect of place of residence further since half of all African people will soon be urban, and more than half of those people will live in slums.

— Richard Lilford, CLAHRC WM Director

References:

  1. Kirkwood BR, Manu A, ten Asbroek AHA, et al. Effect of the Newhints home-visits intervention on neonatal mortality rate and care practices in Ghana: a cluster randomised controlled trial. Lancet. 2013; 381(9884): 2184-92.
  2. Prost A, Colbourn T, Seward N, et al. Women’s groups practising participatory learning and action to improve maternal and newborn health in resource-limited settings: systematic review and meta-analysis. Lancet. 2013; 381(9879): 1736-46.

 

Abnormal Glandular Cells on a Smear Test: What Do They Mean?

When a woman has a smear test, two types of cell are sampled – squamous cells from the ectocervix, and glandular cells from the endocervix:

054 DC - Abnormal Glandular Cells

When abnormal cells are found they are mostly squamous cells from the ectocervix. But about one time in twenty they are glandular cells from the endo-cervix. The squamous cells, meanwhile, can have either a high-grade or a low-grade abnormality.

A recent Swedish study followed up over three million women who had had a cervical smear.[1] Over 15 years, over 3% of women with high-grade squamous cell abnormality and nearly 1% with low-grade squamous cells abnormality developed invasive cancer – almost always squamous cell cancer. But what about the much smaller population of women with abnormal glandular cells? Here about 2.5% developed cancer over the follow-up period – usually adenocarcinoma. The risk is greatest over the first few months, thereafter accumulating very gradually. The high risk post-smear is, of course, because the smear is the trigger for the biopsy. The very slow progression rate over subsequent years should be highly reassuring for any woman who has had an abnormal smear result. As cone biopsy is associated with worse pregnancy outcomes, the CLAHRC WM Director would advise women with abnormal glandular cells to have regular smear test and complete their families as soon as possible. Testing for different types of papilloma virus may help determine whether the risk is higher or lower than the above risk of 2.5%. This study shows the value of long-term registry data of the sort Sweden is famous for.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Wang J, Andrae B, Sundström K, et al. Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study. BMJ. 2016; 352: i276.

Exposure of the Baby to a Rich Mixture of Coliform Organisms from the Birth Canal.

Previous research has pointed out that a good draught of such organisms seem to be healthy, as children brought up after delivery by Caesarean have a much higher incidence of atopic allergic reactions than those delivered through the birth canal.[1] Moreover, the colonic microbiome differs across babies born by vaginal vs. abdominal routes. Many have taken this evidence to heart, and have started to paint the baby’s face with a swab marinated in vaginal secretions. A balanced editorial in the BMJ [2] says that such a practice should not be recommended lest the baby be inoculated with less benign organisms called Beta Strep, resident in some vaginas. But if a woman wishes to practice such a procedure, she should not be inhibited from doing so, pending a trial big enough to determine the net long-term effects.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Neu J, & Rushing J. Cesarean versus Vaginal Delivery: Long term infant outcomes and the Hygiene Hypothesis. Clin Perinatol. 2011; 38(2): 321-31.
  2. Cunnington AJ, Sim K, Deierl A, et al. “Vaginal seeding” of infants born by caesarean section. BMJ. 2016; 352: i227.

 

Does Breastfeeding Protect Against Type 2 Diabetes in Women Who Have Had Gestational Diabetes?

Pregnancy is a kind of metabolic stress test for risk of diabetes later in life; the life time risk of type 2 diabetes mellitus is a whopping seven-fold increase above controls in women with gestational diabetes. Breast feeding has positive metabolic effects and promotes weight loss. It is therefore highly plausible that breastfeeding would reduce the risk of type 2 diabetes in women whose pregnancies were complicated by gestational diabetes. However, there have been surprisingly few studies of this hypothesis, and those that have been done have mostly been retrospective and did not collect enough information to adjust for all known confounders. The small number of prospective studies have been too few to examine for risk-adjusted associations between exposure and outcome. This deficiency in the literature has now been corrected by a mighty study of 1000 women with gestational diabetes, intensively investigated at base line, and followed-up for two years after delivery.[1] The results, after extensive adjustment, are clear. Breastfeeding is associated with a large decrease (approximately 50%) in incidence of diabetes over follow-up, and there is a strong positive association between duration of breastfeeding and degree of protection.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Gunderson EP, Hurston SR, Ning X, et al. Lactation and Progression to Type 2 Diabetes Mellitus After Gestational Diabetes Mellitus. Ann Intern Med. 2015; 163: 889-98.

Low Fertility Rates are Exaggerated

This extremely important paper argues that fertility rates in high-income countries are not as low as normally quoted.[1] Indeed, contemporary very low rates (e.g. 1.3 children per woman in Italy) are partly an artefact of delayed pregnancy, not reduced pregnancy. The standard method that imputes age specific rates from earlier cohorts underestimate life-time fertility over the epoch when age of first pregnancy is increasing. This means that dependency ratios are not as low as had been assumed hitherto. You can see why the CLAHRC WM Director thought this paper very important.

— Richard Lilford, CLAHRC WM Director

References:

  1. Myrskylä M, Goldstein JR, Cheng YA. New Cohort Fertility Forecasts for the Developed World: Rises, Falls, and Reversals. Pop Develop Review. 2013; 39(1): 31-56.