- This study followed women who booked home births in the UK in 1994 and matched them to similar women who booked hospital births. - Outcomes were recorded for 5,971 home birth women and 4,724 matched hospital birth women. The groups were low-risk and well-matched. - Planning a home birth was found to halve the chances of assisted or caesarean births compared to planning a hospital birth. Home births also had less reported high blood pressure and less stressful antenatal care. - However, bias may exist since home birth women tended to be more educated/affluent and high-risk women who transferred care were excluded.

1. Name : Tejal R Lakhan
MSc Biostatistics and Demography

2. CASE CONTROL STUDY

3. MACMOHAN’S 1981 STUDY OF COFFEE
AND PANCREATIC CANCER
Brian MacMahon (1923 2007) was a British American epidemiologist
who chaired the Department of Epidemiology at Harvard from 1958
until 1988.
 In 1981, he published a paper in the New England Journal of
Medicine, a case control study on coffee drinking and pancreatic
cancer.
The study concluded that "coffee use might account for a substantial
proportion of the cases of this disease in the United States."

4. WHO WERE CASES AND CONTROLS ?
 The cases were patients with a histologically confirmed diagnosis
of pancreatic cancer in 11 Boston and Rhode Island hospitals from
1974 to 1979.
 Controls were the patients with other diseases who were
hospitalized by the same physicians who had hospitalized the
cases.
One finding in this study was an apparent dose response
relationship between coffee drinking and cancer of the pancreas.

5.  When such a relationship is observed , it is difficult to know whether the
disease is caused by the coffee drinking or by some factor closely related to
coffee drinking.
 Because smoking is a known risk factor for the cancer of the pancreas.
 And because coffee drinking is closely related to cigarette smoking .

6.  The authors analysed the data after stratifying for smoking history.
 The relationship with coffee drinking held both for current smokers and for
those who had never smoked .
The association was not affected by controlling for cigarette use.
What MacMohan and co-workers found was that the level of coffee
drinking in cases was greater than the level of coffee drinking in controls.

7.  The investigators would like to be able to establish that the level of
coffee drinking observed in the controls is what would be expected in
the general population without pancreatic cancer .
 And cases demonstrate excessive coffee drinking .

8. But the problem is :
Which physicians are most likely to admit patients with cancer of
pancreas to the hospital ?
Gastroenterologists are often the admitting physicians.
Many of there other hospitalized patients ( who served as controls )
also have gastrointestinal problems.

9.  The persons who served as controls may very well have reduced their
intake of coffee, either because of a physician’s instructions or because
of their own realization that reducing their coffee intake could relieve
their symptoms.
 Thus, the observed difference in coffee drinking between pancreatic
cancer cases and controls may not necessarily have been the result of
cases drinking more coffee than expected , but rather of the controls
drinking less coffee than expected.

10.  MacMohan and his colleagues subsequently repeated their analysis
but separated controls with gastrointestinal illness from controls with
other conditions .
 They found that the risk associated with coffee drinking was indeed
higher when the comparison was with controls with gastrointestinal
illness but that the relationship between coffee drinking and pancreatic
cancer persisted, at a lower level ,even when the comparisons was
with controls with other illness.
 MacMahon's group, failed to confirm the association

11.  When a difference in exposure is observed between cases and
controls , we must ask whether the level of exposure observed in the
controls is really the level expected in the population in which the
study was carried out or whether perhaps given the manner of
selection .
 The controls may have particularly high or low level of exposure that
might not be representative of the level in the population in which the
study was carried out.
CONCLUSION

12. COHORT STUDY

13. DUTCH FAMINE STUDY ( EFFECTS OF
STARVATION )
The winter of 1944–45 is known as the ‘Hunger Winter’ in The
Netherlands, which was occupied by the Germans in May 1940.
It was a famine that took place in the German-occupied part of the
Netherland, especially in the densely populated western provinces north of
the great rivers, during the winter of 1944-45, near the end of World War 2.

14. HISTORY
Despite the war, nutrition in The Netherlands had generally been adequate up to
October 1944.
 Thereafter, food supplies became increasingly scarce.
By November 26, 1944. Widespread starvation was seen especially in the cities of
the western Netherlands.
Food supplies were restored immediately after liberation on May 5, 1945.
 On the basis of these historical data it was possible to accurately define the
beginning and the end of the famine period

15.  The famine affected fertility, weight gain during pregnancy, maternal blood
pressure, infant size at birth and central nervous system development.
The reduction in fertility was greater among manual workers than among
those in other occupations.
 A decline in mean birth weight of 300 g was seen among those exposed to
maternal undernutrition during the third trimester.
the famine created what can be regarded as a ‘natural experiment’ in which
exposure to famine is assigned based on an individual's time and place of
birth.
 This design was used to examine how maternal undernutrition during
specific gestational time windows may affect the subsequent life course of
offspring who experienced the famine in-utero.

16. What does the study cover?
The primary aims of the study are
 (i) to examine whether changes in maternal nutrition in pregnancy affect the risk among
offspring for metabolic and cardiovascular disease in adulthood.
(ii) to identify critical time windows of pregnancy at which fetal programming might
occur.
 (iii) to document to what extent the time windows of prenatal programming might differ
with respect to the adult risk of Type 2 diabetes mellitus, blood pressure and obesity and
 (iv) to validate the performance of selected morphological measures of the hand (e.g.
fingertip ridge-count differences and digit-length ratios) as specific markers of
disturbances in early gestation. The study also included measures of other outcomes of
interest such as cognitive status and depressive symptoms.

17. Who is in the sample?
 3307 live-born singleton births at three institutions in famine-exposed
cities (the midwifery training schools in Amsterdam and Rotterdam and the
university hospital in Leiden) were identified.
(i) all 2417 births between February 1, 1945 and March 31, 1946 (infants
whose mothers were exposed to the famine during or immediately
preceding that pregnancy) and
(ii) a sample of 890 births from 1943 and 1947 as time controls (infants
whose mothers did not experience famine during this pregnancy). The
sample of controls included an equal number of births for each month,
allocated across the three institutions according to their size.

18.  At the time the large majority of deliveries (70% or more) were scheduled
to occur at home.
The client mix at the two midwifery schools consisted of low-risk
pregnancies to women of lower socioeconomic status whose home
environment was unsuitable for delivery.
The client mix in Leiden also included higher-risk pregnancies identified
during prenatal care and emergency admissions following complications of
labour or delivery.
Whenever possible, we also enrolled a same-sex sibling of each member of
the birth series as controls. For participants recruited as siblings, no
information from prenatal or delivery records is available.

19. How often have they been followed up?
Members of the study population were traced to their current address
in 2003. A telephone interview and medical examination were
conducted in 2003–05.

20. What has been measured?
Birth records
They extracted the following information from the pregnancy and delivery
medical records:
mother's and infant's names; address; age at delivery; occupation; religion;
last menstrual period (LMP); gravidity and parity; lifetime number of
spontaneous abortions; date of first prenatal visit; weight, height and blood
pressure at prenatal visits; date and time of delivery; maternal postpartum
weight (two clinics only): obstetrical presentation; mode of delivery; sex;
birth weight; crown-to-heel length; head circumference; placental weight
(two clinics only) and vital status at discharge. Abstraction of records of the
3307 birth records was completed in May 2003.

21. They submitted the names and addresses at birth to the local population
registers with a request to provide a current address. They then invited by
mail all traced members of the birth cohort to participate in the study.
they conducted a telephone interview, followed by a clinical examination at
the Leiden University Medical Center. All study protocols and materials for
data collection were approved by the human subjects committees of all the
participating institutions.
 Participants provided oral consent at the start of the interview and written
informed consent at the start of the clinical examination for all study
procedures.

22. Telephone Interview
The telephone interview included questions on sociodemographic
characteristics and socioeconomic status.
 In addition, they collected information on health and reproductive history,
on current health status, on prevalent medical conditions such as stroke and
cardiac problems, on high blood pressure and on diabetes.
They also collected information on smoking and drinking habits. For
selected conditions, participants were asked for information on their parents
and siblings.

23. Clinical examinations
Participants were asked to fast overnight before a morning appointment;
over 95% complied with this request.
On their arrival at the clinic, they first obtained written informed consents
for study examinations and blood collection and storage, including consent
for later study of DNA.
They then measured blood pressure with an automated blood pressure
monitor with digital readout, recorded three successive electrocardiogram
(ECG) readings and drew a blood sample to obtain fasting measures of
lipids, glucose and insulin.

24. a standardized food frequency questionnaire.
a physical activity questionnaire.
a neuropsychological test battery for cognitive function , visual verbal
learning, colour scale performance (Stroop), and verbal fluency . a quality-
of-life assessment .
Upon completion, all questionnaires were checked by study staff and
participants were asked to provide missing information where necessary.

25. All collected study information was entered twice into a database (double
entry keypunching) and any discrepancies were resolved by re-checking
against the original coding sheets.
In all, they completed the clinical examination in 94% (971/1031) of the
people interviewed by telephone.
 Full details of causes of attrition for eligible participants to interview and
clinical examinations, together with comparisons of perinatal characteristics
between those who were included in these follow-up data collections and
those who could not be are provided below.

26. Defining exposure to the famine
To define exposure to the famine for all selected participants, they have
used an ecological measure to classify stage of gestation in relation to the
available food rations.
Although maternal nutrition in pregnancy cannot be ascertained at the
individual level, evidence for the impact of the famine on morbidity and
mortality at the population level is abundant. With regard to nutrition in
pregnancy, they have shown that many women actually lost weight in
pregnancy.

27. Exposure by date of last menstrual period
 They used the date of last menstrual period (LMP) listed on the birth record
to define the start of gestation unless it was missing or implausible (12%).
Exposure by date of birth
 In contrast to this prospective approach, in most studies of the Dutch famine
to date, prenatal exposure to famine has been defined relative to date of
birth

28. It was found that the children of pregnant women exposed to famine were
more susceptible to diabetes , obesity, cardiovascular disease, and other
health problems.
Moreover, the children of the women who were pregnant during the famine
were smaller, as expected. However, surprisingly, when these children grew
up and had children those children were thought to also be smaller than
average .

29. The discovery of the cause of coeliac disease may also be partly attributed
to the Dutch famine. With wheat in very short supply there was an
improvement at a children's ward of Coeliac patients. Stories tell of the first
precious supplies of bread being given specifically to the (no longer) sick
children, prompting an immediate relapse.
 Thus in the 1940s the Dutch paediatrician was able to corroborate his
previously researched hypothesis that wheat intake was aggravating Coeliac
disease. Later Dicke went on to prove his theory.

30. Audrey Hepburn spent her childhood in the Netherlands during the famine
and despite her later wealth she had lifelong negative medical
repercussions. She suffered from anaemia, respiratory illnesses, and edima
as a result. Also, her clinical depression later in life has been attributed to
malnutrition.
Subsequent academic research on the children who were affected in the
second trimester of their mother’s pregnancy found an increased incidence
of schizophrenia in these children .Also increased among them were the
rates of schizotypal personality and neurological defects.

31. Strengths and weaknesses
Exposure
With archived records of the weekly food rations distributed in the affected
areas, there is no need to use birth weight as a proxy measure of maternal
nutrition in pregnancy.
In this study, they assigned exposure based on the date of mothers’ LMP from
the birth record, adjudicated where necessary.
Study population
They have shown that normally the loss to follow-up is low (11% or less) when
infants are traced from their famine birth records to their current address in The
Netherlands .

32. Sibling controls
These controls were chosen to reduce the potential for bias related to
family-level factors with an effect on health outcomes that is
independent of the exposure of interest.
 This is important in light of the strong associations between
socioeconomic status of the family and fertility during the famine,
with stronger declines in fertility among manual vs non-manual
occupations.

33. Intermediary variables over the life course
Although extensive recorded information is available from the time of birth
and from the time of examination , there is no source for intermediary data
points except for the individual interview, in which we ascertained recalled
weight at age 20 and 30 and collected a medical history.
Within The Netherlands health care system, well baby clinic records were
collected for all study participants and reports from annual school health
examinations were collected through adolescence that included height,
weight and selected medical problems.

34. COHORT STUDY

35. National Birthday Trust - Report of the
Confidential Enquiry into Home Births
This is probably the most comprehensive study of home birth ever
undertaken in the UK.
 It attempted to follow all women who booked a home birth in the UK in
1994.
Midwives recorded outcomes for 5971 women who were booked for home
births at 37 weeks' gestation, and they tried to find a matching woman from
their practice who was as similar as possible to the home birth mother, but
was booked to deliver in hospital. In some cases an appropriate matching
hospital booking could not be found, so the hospital group only contained
4724 women.

36. The women were matched for age (within 5 yrs), number of previous
children, where they lived, and past obstetric history.
Thus, low-risk mothers were compared with other low-risk mothers, and
the overall sample in the home birth group could be accurately compared to
that in the matching group. The overall group profile was low-risk.
 For all outcomes, planned home births were compared with planned
hospital births, so the data for planned home births include those births
which occurred at home, and transfers to hospital. Separate data for
transfers is also provided.
First-time mothers made up 16% of the group, whilst 84% were expecting
second or subsequent children. Mothers who had a previous Caesarean
made up 1% of the home birth group, and 3% of the hospital group.

37. Possible Bias
 Women planning home births tend to be more educated and more affluent
than those in the hospital group, which would make them slightly lower-risk
 The home birth group had less incidence of high blood pressure at 37
weeks,
and the birth - which could be because midwife antenatal care was less
stressful than hospital antenatal care, but could also be because women who
developed high blood pressure before 37 weeks (and transferred their
booking to the hospital) would not be included in the home birth group, but
would possibly be included in the hospital group .

38. The Labour/Birth
Planning a home birth halved the chances of mothers in this study having
assisted or caesarean births. The overall rate of these events was very low,
because mainly only low-risk women booked for a home birth.
The authors note that
'The hypothesis that social and environmental factors can affect progress of
labour and mode of delivery is strongly supported by experimental
evidence. A systematic review of randomized controlled trials shows that
continuous professional support during labour is associated with a reduced
incidence of Caesarean section and instrumental delivery. In the light of this
evidence it is easy to accept that some women may labour better in their
own homes.

39. Home births, including transfers, were less likely to involve post-partum
haemorrhage. Home birth mothers had fewer episiotomies but more first-
degree perineal tears. Second-degree tears occurred at the same rate in both
groups. All cervical tears occurred in the hospital group.
One set of twins were born at home, with no complications; one was cephalic
and the other breech.
Planned home births
Planned hospital births
(including transfers)
Spontaneous vaginal delivery 94.70% 90.20%
Assisted (forceps, ventouse) 2.40% 5.40%
Caesarean 2.00% 4.10%

40. Previous Caesareans, Home Deliveries and
Previous Assisted Deliveries
Of the women planning home birth who had given birth before, 9.7% had
previous assisted deliveries and 1.4% (53 women) had previous caesareans.
The transfer rate amongst the previous assisted delivery group was 15.6%,
and among the previous caesarean group it was 28%; so 72% of these
women had a home deliveries.
The study does not give data on the proportion of the women with previous
caesareans who had another caesarean after transfer, but the overall
caesarean rate for women transferred from home to hospital was 11.2% .

41. Transfer Rates
16% of women booked for a home birth transferred to hospital, 60% of first-time mothers who had
planned to deliver at home, did so, and 40% transferred. 90% of multigravida who had planned to
deliver at home, did so, and 10% transferred.
Some of these transfers occurred before labour actually started, whilst others occurred in labour.
The single largest reason for transfer was slow or no progress, accounting for 37.2% of transfers.
Premature rupture of membranes accounted for 24.8% of transfers, and most of these occurred
before labour started. Foetal distress accounted for 14.8% of transfers. There was one cord
prolapse.
The number of mothers and babies who transferred was 769 this group included two stillbirths and
two neonatal deaths.
The transferred home births had the worst outcome rate of all three categories (planned and born at
home, planned and born in hospital, planned home but born hospital) for labour interventions and
condition of the baby. Clearly, as transfer generally only occurs if there is a problem, this group
would be the highest-risk component of the study.

42. Pain Relief
Women who planned a home birth were much less likely to use drugs for
pain relief, than women who planned a hospital birth. The drugs most
commonly available at home births in the UK are Entonox , and Pethidine .
In some areas these substances are taken routinely to all home births, and in
others they are available only on request.
The table shows the forms of pain relief used, as reported by midwives. It's
also worth remembering that what one midwife might report as 'relaxation',
another might report as 'no pain relief'

43. Pain Relief
Planned home
Planned hospital
Home births Transfers from
overall (born at home) home to hospital
Drugs
Entonox 52.60% 72.10% 50.10% 65.80%
Pethidine/Demerol 7.50% 30.30% 4.30% 23.70%
Epidural 2.8% (all transfers) 11.30% 0 17.90%
Spinal Block 0.70% 1.30% 0 4.10%
Non-drug methods
Relaxation 49.00% 30.10% 50.30% 43.10%
TENS 22% 15.40% 20.60% 28.80%
Warm water 24.40% 8% 24.50% 24%
Aromatherapy 5.20% 0.90% 5.20% 5.10%
Homeopathy 3.40% 0.30% 3.30% 4%
Acupuncture 0.60% 0 0.50% 0.90%
None 17.10% 8.60% 18.80% 7.90%

44. The Baby
Babies planned for home birth were less likely to be in bad condition (low APGAR score) at birth,
even including those transferred to hospital.
At 1 minute, 5.2% of the planned home babies had APGAR scores below 7, compared to 9.3% of
the planned hospital babies.
 At 5 minutes, 0.7% of both groups had scores below 7.
Babies planned for home birth were less likely to have any of these interventions.
Again, the rate for transfers was slightly higher than the rate for planned hospital births, but the
overall planned home birth rate was lower.

45. The most common birth injury was bruising, which affected 0.6% of the planned
home babies and 1.4% of the planned hospital babies.
The overall rate of stillbirths and neonatal deaths was very low for the whole
study - 5 stillbirths and neonatal deaths in the 5,971 planned home births and 5 in
the 4,724 planned hospital births, compared to the national rate of 8 per 1,000
births. The researchers concluded that the death rate in both groups was too low to
allow meaningful comparison between the two groups.
Planned home Planned hospital
Suctioned 11.30% 18.00%
Bag and mask 5.60% 9.10%
Intubation 0.60% 0.80%

46. Baby feeding
Exclusive breastfeeding rates 48 hours after birth were 80% in the home
birth group and 58.1% in the planned hospital group; six weeks later, the
figures were 65% and 44.
However, breastfeeding rates for the transferred home births were almost
identical to the home deliveries in all categories, including the mother's
assessment of whether the first feed went well. The transferred mothers and
babies had the most difficult deliveries on average, so this suggests a high
level of commitment from these women to breastfeed despite the
circumstances.